Angiogenesis is important in the pathophysiology of endometriosis, a condition characterized by implantation of ectopic endometrium in the peritoneal cavity. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in physiological and pathological angiogenesis, and elevated levels of VEGF are found in peritoneal fluid of patients with endometriosis. Our aim was to investigate the site of expression and regulation of VEGF in endometriosis. VEGF immunoreactivity was found in tissue macrophages present in ectopic endometrium and in activated peritoneal fluid macrophages. Macrophage activation was highest in women with endometriosis, and media conditioned by peritoneal fluid macrophages from these women caused a VEGF-dependent increase in endothelial cell proliferation above that seen from normal women. Peritoneal fluid macrophages secreted VEGF in response to ovarian steroids, and this secretion was enhanced after activation with lipopolysaccharide. Peritoneal fluid macrophages expressed receptors for steroid hormones. VEGF receptors flt and KDR (kinase domain receptor) were also detected, suggesting autocrine regulation. During the menstrual cycle, expression of flt was constant but that of KDR was increased in the luteal phase, at which time the cells migrated in response to VEGF. KDR expression and the migratory response were significantly higher in patients with endometriosis. This study demonstrates that activated macrophages are a major source of VEGF in endometriosis and that this expression is regulated directly by ovarian steroids. ( J. Clin. Invest. 1996. 98:482-489.)

Summary This analysis, of 2483 patients with acute myeloid leukaemia (AML) aged 60+ years entered into two UK trials, was performed to determine the baseline parameters related to survival and to develop a risk index. The Medical Research Council (MRC) AML11 trial (n = 1071) was used to develop the index; this was validated using data from the Leukaemia Research fund (LRF) AML14 trial on 1137 intensively (AML14I) and 275 non‐intensively (AML14NI) treated patients. In AML11, cytogenetic group, age, white blood count, performance status and type of AML (de novo, secondary) were all highly significantly related to prognosis in multivariate analysis. The regression coefficients were used to define good, standard and poor risk groups, with 1‐year survival of 53%, 43% and 16% respectively (P < 0·0001). The risk index showed very good discrimination in both AML14I and AML14NI (both P < 0·0001), thereby providing validation, although survival in all groups was very poor in AML14NI. The risk factors for survival in older AML patients were similar to those in younger ones and discrimination of patient groups with relatively good to very poor prognosis was possible. These risk groups apply to both intensively and non‐intensively treated patients. Randomized trials of intensive versus non‐intensive therapy are needed to determine which types of patient should be given which type of treatment.

Several chemotherapy schedules achieved similar remission rates and OS. Four courses of chemotherapy are adequate, but the addition of transplantation as a final course does not improve OS. New agents are required to enhance conventional chemotherapy.

No abstract

Antifungal prophylaxis with itraconazole effectively prevents proven invasive fungal infections and-shown for the first time for antifungal prophylaxis-reduces mortality from these infections and the rate of invasive Aspergillus infections in neutropenic patients with hematologic malignancies. Adequate doses of the oral cyclodextrine solution (at least 400 mg/d) or i.v. formulations (200 mg/d) of itraconazole are necessary for these effects.

No abstract

Summary.Fluconazole is widely used as antifungal prophylaxis but it is ineffective against Aspergillus. Itraconazole has a broader spectrum of activity but the capsules give erratic bioavailability in neutropenic patients. We compared itraconazole oral solution (which has an improved pharmacokinetic profile) with fluconazole for antifungal prophylaxis.Adults with haematological malignancies receiving chemotherapy or bone marrow transplants were randomly allocated 5 mg/kg/d itraconazole (itra) solution (288 episodes) or 100 mg fluconazole suspension (flu) (293 episodes) from before the onset of neutropenia until neutrophil recovery or suspected fungal infection. Outcomes were assessed by independent reviewers unaware of the prophylaxis allocation.More proven systemic fungal infections occurred in flu (Aspergillus four, Candida tropicalis one, C. krusei one) than itra (C. albicans one) and more of these were fatal (four versus nil). This difference reached statistical significance when first study episodes were considered separately (six flu versus nil itra, P ¼ 0·03). Significantly more deaths of presumed fungal origin occurred in flu than itra (seven versus nil, P ¼ 0·024). There were significantly more cases of proven aspergillosis in flu than itra (six versus nil, P ¼ 0·038, 5/6 cases were fatal) if those occurring outside the study period are included. Significantly more patients receiving flu required amphotericin B (58 v 39, P ¼ 0·043) but this may have been affected by the fact that the study was not blinded. There were 11 proven mucosal candidal infections in flu and four in itra.Itraconazole solution and fluconazole provide effective prophylaxis against Candida but itraconazole affords greater protection against fatal aspergillosis.

We have treated 52 patients with chronic lymphocytic leukaemia (CLL) with fludarabine; 12 developed severe autoimmune haemolysis. Only three had a previous history of haemolytic anaemia. Six out of eight patients retreated with fludarabine after control of their haemolysis developed an exacerbation of the haemolytic anaemia. The cause of autoimmune phenomena in CLL is not known, but our findings reinforce the view that they are caused by a disturbance in immunoregulatory T cells. Fludarabine is a known suppressor of T-cell function.