Interaction of liposomes with human leukocytes in whole blood.

The uptake of multilamellar liposomes into human leukocytes in whole blood in vitro was evaluated on the basis of the cellular association of liposomal markers (3H-labelled cholesterol, lipid phase; [14C]inulin, aqueous phase). The entry of liposomes into human blood leukocytes was linear for 60 min and was mediated by a saturable mechanism displaying affinity constants of 0.28 +/- 0.17 and 0.16 +/- 0.05 mM liposomal lipid (means +/- S.E.) for liposomal lipid and aqueous phase markers, respectively. Amicon filtration analysis of incubation mixtures containing blood and liposomes (phosphatidylcholine:dicetyl phosphate:cholesterol, 70:20:10) showed that 34% of [14C]inulin was lost (neither liposome-associated nor cell-associated) after 60 min. By preincorporating sphingomyelin (35 mol%) into multilamellar liposomes, the leakage of the model aqueous phase marker inulin was reduced to 8% after 60 min, thus enhancing the drug carrier potential of liposomes in blood. As a consequence of their interaction with liposomes, the polymorphonuclear leukocytes in whole blood decreased in apparent buoyant density, while maintaining their viability. These results indicate that blood leukocytes in their natural milieu of whole blood are capable of interacting with, and taking up multilamellar liposomes.

Risk of diagnosis of ovarian cancer after raised serum CA 125 concentration: a prospective cohort study.

OBJECTIVE: To determine the risk of invasive epithelial ovarian cancer and fallopian tube cancer associated with a raised concentration of the tumour marker CA 125 in asymptomatic postmenopausal women. DESIGN: Serum CA 125 concentration was measured annually in study participants for one to four years. Participants with a concentration > or = 30 U/ml were recalled for abdominal ultrasonography. Follow up was by annual postal questionnaire. SETTING: General practice, occupational health departments, ovarian cancer screening unit in a teaching hospital. SUBJECTS: 22,000 volunteers, all postmenopausal women > or = 45 years of age; recruited between 1 June 1986 and 1 May 1990. INTERVENTION: Surgical investigation if the ultrasound examination was abnormal. MAIN OUTCOME MEASURES: Cumulative and relative risk of developing an index cancer (invasive epithelial cancer of the ovary or fallopian tube) after a specified CA 125 result. RESULTS: 49 index cancers developed in the study population during a mean follow up of 6.76 years. The overall cumulative risk of developing an index cancer was 0.0022 for the entire study population and was lower for women with a serum CA 125 concentration < 30 U/ml (cumulative risk 0.0012) but was appreciably increased for women with a concentration > or = 30 U/ml (0.030) and > 100 U/ml (0.149). Compared with the entire study population the relative risk of developing an index cancer within one year and five years was increased 35.9-fold (95% confidence interval 18.3 to 70.4) and 14.3-fold (8.5 to 24.3) respectively after a serum CA 125 concentration > or = 30 U/ml and 204.8-fold (79.0 to 530.7) and 74.5-fold (31.1 to 178.3) respectively after a concentration > or = 100 U/ml. CONCLUSION: CA 125 is a powerful index of risk of ovarian and fallopian tube cancer in asymptomatic postmenopausal women.

[Mucocele of the appendix in highly differentiated adenocarcinoma]. / Mukozele der Appendix bei hochdifferenziertem Adeno-Karzinom.

A patient 69 years old had been admitted at the University Women's Hospital Berlin because of a suspected ovarian tumour. Outside a computed tomography was done. In the small pelvis a tumour partly cystic and partly solid at the right side could be confirmed sonographically. Because this an operation was indicated. After opening the abdomen the internal female genital organs were in conspicuous with the exception of extensive adhesions. Histologically we found a mucocele of the vermiform appendix with a highly differentiated adenocarcinoma. All tissue layers were infiltrated and perforated. This combination of findings is very seldom, because carcinomas of the appendix could be proved only in 0.01 per cent of all appendectomies.

[Lactate dehydrogenase isoenzymes in the growth of heart cells]. / Laktaatdehidrogenase isosieme in hartselontwikkeling

As part of a detailed biochemical study of developing and growing heart cells, the protein- or cell-specific activities of lactate dehydrogenase isozymes were determined in cultured neonatal hamster heart cells and in intact hearts of hamster embryos and neonates. Evidence for differentiative growth of heart cells in both systems was obtained, but the characteristic in vivo isozyme shift from species rich in M subunits to those containing mainly H subunits was reversed in the cultured cells, suggesting that controls normally determining this pattern change might be absent in the conditions of in vitro cultivation.