Burkitt's lymphoma in British adults: clinical features and response to chemotherapy.

Eight British adults with tumours histologically and cytochemically identical to African Burkitt''s lymphoma are described. In each case there was an acute clinical onset and similar tumour distribution, with involvement of the intra-abdominal organs, bone marrow and central nervous system. Jaw tumours were only present in 3 cases, and were never gross. Four patients presented as acute leukaemia. Combination chemotherapy and cranial irradiation were used to eradicate disease, but complete remissions were obtained in only 3 patients, and survival of over 1 year in only 2. The remainder died with disease present, less than 5 months from diagnosis.     

Variable incidence of cyclosporine and FK-506 neurotoxicity in hematopoeitic malignancies and marrow conditions after allogeneic bone marrow transplantation

Introduction: This study examines whether malignant disease under treatment influences the incidence of cyclosporine or FK-506 neurotoxicity after myeloablative conditioning and allogeneic bone marrow transplantation (allo-BMT). Methods: Review of 290 patients who received myeloablative conditioning prior to allo-BMT and cyclosporine/FK-506 identified 21 (7.2%) patients with neurotoxicity confirmed by computed tomography or magnetic resonance. Underlying malignancy necessitating allo-BMT included leukemias (67%), lymphoma (10%), myelodysplastic syndrome (10%), and multiple myeloma (MM). Frequency of neurotoxicity by disease was compared. Results: The highest incidence of neurotoxicity was present with MM (25%), whereas the lowest incidence was present with lymphoma (2.7%). Other diseases demonstrated intermediate incidence, including acute leukemias (10%), myelodysplastic syndrome (6.4%), and chronic myelogenous leukemia (4.9%). Conclusion: Cyclosporine/FK-506 neurotoxicity varied according to the underlying malignancy. The variable susceptibility to the development of neurotoxicity in this population may depend on the interaction of host vasculature with disease specific factors. Understanding the cause of neurotoxicity could improve survival after allo-BMT.     

Mutation of CEBPA in familial acute myeloid leukemia

We describe a family in whom three members affected by acute myeloid leukemia (AML) had an identical, 212delC mutation in CEBPA, the gene encoding the granulocytic differentiation factor C/EBPalpha. Unaffected family members did not have this mutation. Latent periods of 10, 18, and 30 years elapsed before the onset of overt leukemia in the three patients. One of them had a second CEBPA mutation, but only at the time of diagnosis. All three patients are currently well, with no abnormalities in the bone marrow. CEBPA mutation is apparently the primary event in the development of AML in this family.     

An investigation of the antioxidant properties and colour of glasshouse grown tomatoes

The colour and the antioxidant content of five different cultivars of tomatoes (Lycopersicon esculentum L.), grown in glasshouses using commercial hydroponic techniques, were measured in freshly harvested tomatoes and after 2 and 5 days of storage in the dark at 15 degrees C. The two cocktail cultivars of tomatoes, Aranca and Flavourine, were the smallest tomatoes but they contained higher dry matter contents compared with the three standard salad cultivars, Excell, Celero and Dutch Chaser. There were significant differences (P < 0.001) in lycopene (the major carotenoid), ascorbic acid and total antioxidant activity in the whole fruit of the five different cultivars evaluated at harvest, while the total phenolic contents were very similar. The lycopene levels of all the cultivars increased significantly (P < 0.001) after storage for 2 and 5 days at 15 degrees C. Overall, the total phenolic content of all the cultivars did not change appreciably after storage at 15 degrees C while the levels of ascorbic acid fell by 12.6% when stored for 5 days in the dark. There was a significant difference (P < 0.001) in the total antioxidant activity between the five different cultivars when freshly harvested; the highest levels of total antioxidant activity were observed in the two cocktail cultivars, Aranca and Flavourine. Antioxidant activity showed different patterns of change depending on cultivar. An increase in the total antioxidant values could be seen in cultivars Dutch chaser and Excell, after storage for 5 days at 15 degrees C. The total antioxidant activity values of Flavourine and Celero fell on storage while the values for stored Aranca were very similar to the values when freshly harvested.The skin colour, as shown by Commission Internationale l'Eclairage (CIE) L*a*b* values of each cultivar were markedly different at harvest even though each cultivar was harvested at the same maturity. The a* value of each cultivar increased significantly (P < 0.001) when they were stored in the dark, for either 2 or 5 days, at 15 degrees C. Regression analysis showed that overall there was no significant relationship (R(2) = 0.14) between the lycopene content and the a* value of all the tomatoes; however, when examined individually, the two cocktail tomatoes Aranca and Flavourine showed strong correlation-R(2) = 0.96 and R(2) = 0.97, respectively. Overall, the (a*/b*)(2) was the most reliable indicator of lycopene concentration (R(2) = 0.96) in the tomatoes examined in this study.     

Focal astrocyte loss is followed by microvascular damage, with subsequent repair of the blood-brain barrier in the apparent absence of direct astrocytic contact

Blood-brain barrier (BBB) breakdown is a feature of cerebral ischaemia, multiple sclerosis, and other neurodegenerative diseases, yet the relationship between astrocytes and the BBB integrity remains unclear. We present a simple in vivo model in which primary astrocyte loss is followed by microvascular damage, using the metabolic toxin 3-chloropropanediol (S-alpha-chlorohydrin). This model is uncomplicated by trauma, ischaemia, or primary immune involvement, permitting the study of the role of astrocytes in vascular endothelium integrity, maintenance of the BBB, and neuronal function. Male Fisher F344 rats given 3-chloropropanediol show astrocytic damage and death at 4-24 h in symmetrical brainstem and midbrain nuclear lesions, while neurons show morphological changes at 24-48 h. Fluorescent 10 kDa dextran tracers show the BBB leaking from 24 h, progressing to petechial haemorrhage after 48-72 h, with apparent repair after 6 days. BBB breakdown, but not the earlier astrocytic death, is accompanied by a delayed increase in blood flow in the inferior colliculus. An ED1 inflammatory response develops well after astrocyte loss, suggesting that inflammation may not be a factor in starting BBB breakdown. This model demonstrates that the BBB can self-repair despite the apparent absence of direct astrocytic-endothelial contact. The temporal separation of pathological events allows pharmacological intervention, and the mild reversible ataxia permits long-term survival studies of repair mechanisms.     

Waldenstrom's macroglobulinemia: a retrospective analysis of 40 patients from 1972 to 2001

From 1972 to 2001 at St. Bartholomew's Hospital 40 untreated Waldenstrom's macroglobulinemia (WM) patients received either chlorambucil (n = 23); cyclophosphamide, vincristine, and prednisolone (CVP) (n = 5); fludarabine-based therapy (n = 5); or other combination chemotherapy (n = 7). Twenty-eight patients (70%) responded to first-line therapy with overall response rates as follows: chlorambucil, 17/23 (74%); CVP, 4/5 (80%); fludarabine-based regimen, 2/5 (40%); other combinations, 5/7 (71%). Twenty patients were treated at progression with chlorambucil, of whom 10 (50%) responded again, 6/13 having had chlorambucil initially, and 4/7 having had other therapy. Although there was a trend towards a survival advantage for patients who responded to chlorambucil, this difference was not statistically significant. At 6 and 11 years, overall survival was 36% v 18% and 15% v 0% for responders and nonresponders, respectively. The overall pattern was the same for patients treated initially with chlorambucil as with other therapy. This retrospective analysis confirms that chlorambucil is an effective first-line agent in WM and has activity when used at subsequent relapse.