Monocytes stimulate fibroblastoid bone marrow stromal cells to produce multilineage hematopoietic growth factors

In previous studies we have found that monocytes produce soluble factors that stimulate human umbilical vein endothelial cells to produce granulocyte-macrophage colony-stimulating activity (CSA), burst- promoting activity (BPA), and megakaryocyte colony-stimulating activity (Meg-CSA) as well as factors that stimulate T lymphocytes and neonatal fibroblasts to produce CSA. To test the hypothesis that monocytes would similarly stimulate the production of hematopoietic growth factors by autologous bone marrow stromal cells, multiply-passaged adherent fibroblastoid cells derived from the bone marrow of normal volunteers were exposed to conditioned media prepared by incubating autologous peripheral blood monocytes in complete medium for three days. When conditioned media from stromal cells incubated in monocyte-conditioned medium were compared with those of stromal cells cultured in the absence of monocyte-conditioned medium, BPA was increased fourfold and CSA was increased more than 30-fold. We conclude that mononuclear phagocytes recruit stromal cells of the marrow to produce multilineage growth factors in vitro. We suggest that these monocyte-derived recruiting activities may play an important role in orchestration of hematopoietic growth factor production by cells of the marrow microenvironment.     

Serotonin metabolism in cluster headache

Despite some evidence of the involvement of the serotonergic system in cluster headache (CH) pathophysiology, the serotonin (5HT) metabolism has so far been poorly studied. The aim of this study was to investigate plasma and platelet levels of 5HT and 5-hydroxyindoleacetic acid (5HIAA) in CH patients in the active period of the disease. Nineteen CH sufferers and 17 sex- and age-matched healthy controls were studied. CH patients showed significantly higher plasma levels of 5HT and 5HIAA compared to controls (5HT: 5.7±6.1 ng/ml vs 0.2±0.2 ng/ml; p =0.02; 5HIAA: 34.7±46.1 ng/ml vs 0.6±0.7 ng/ml; p =0.004). In platelet 5HT levels were slightly reduced in CH patients in comparison with those of control subjects (662.4±522.3 ng/10⁻⁸ platelets vs 832.1±587.9 ng/10⁻⁸ platelets; n.s.) and 5HIAA levels resulted significantly lower in CH sufferers than in control subjects (3.2±2.6 ng/10⁻⁸ platelets vs 6.7±4.8 ng/10⁻⁸ platelets; p =0.04). Our data suggest that CH is characterized by an increase of plasma serotonergic metabolism that could reflect an involvement of the central serotonergic system in the pathogenesis of CH.     

Impact of improved glycaemic control on rates of hypoglycaemia in insulin dependent diabetes mellitus

Increased emphasis on strict glycaemic control of insulin dependent diabetes mellitus (IDDM) in young patients may be expected to cause increases in rates of significant hypoglycaemia. To evaluate whether this is the case for a large population based sample of IDDM children and adolescents rates of severe (coma, convulsion) and moderate (requiring assistance for treatment) hypoglycaemia were studied prospectively over a four year period. A total of 709 patients were studied yielding 2027 patient years of data (mean (SD) age: 12.3 (4.4); range 0-18 years, duration IDDM: 4.9 (3.8) years). Details of hypoglycaemia were recorded at clinic visits every three months when glycated haemoglobin (HbA1c) was also measured. Overall the incidence of severe hypoglycaemia was 7.8 and moderate was 15.4 episodes/100 patient years. Over the four years mean (SD) clinic HbA1c steadily fell from 10.2 (1.6)% in 1992 to 8.8 (1.5)% in 1995. In parallel with this there was a dramatic increase in the rate of hypoglycaemia, especially in the fourth year of the study, when severe hypoglycaemia increased from 4.8 to 15.6 episodes/100 patient years. This increase was particularly marked in younger children (< 6 years) in whom severe hypoglycaemia increased from 14.9 to 42.1 episodes/100 patient years in 1995. It is concluded that attempts to achieve improved metabolic control must be accompanied by efforts to minimise the effects of significant hypoglycaemia, particularly in the younger age group.     

Potential environmental determinants of physical activity in adults: a systematic review

The objective of this systematic review of observational studies was to gain insight into potential determinants of various types and intensities of physical activity among adult men and women. Studies were retrieved from Medline, PsycInfo, Embase and Social scisearch. The ANGELO framework was used to classify environmental factors. In total, 47 publications were identified. Social support and having a companion for physical activity were found to be convincingly associated with different types of physical activity [(neighbourhood) walking, bicycling, vigorous physical activity/sports, active commuting, leisure-time physical activity in general, sedentary lifestyle, moderately intense physical activity and a combination of moderately intense and vigorous activity]. Availability of physical activity equipment was convincingly associated with vigorous physical activity/sports and connectivity of trails with active commuting. Other possible, but less consistent correlates of physical activity were availability, accessibility and convenience of recreational facilities. No evidence was found for differences between men and women. In conclusion, supportive evidence was found for only very few presumed environmental determinants. However, most studies used cross-sectional designs and non-validated measures of environments and/or behaviour. Therefore, no strong conclusions can be drawn and more research of better quality is clearly needed.     

Chimiothérapie adjuvante du cancer du sein du sujet âgé

Résumé: Malgré une incidence croissante du cancer du sein dans la population agée, les données spécifiques prospectives concernant sa prise en charge après 70 ans, tout particulièrement pour les indications de chimiothérapie adjuvante, sont rares dans la littérature, gênant l’application de recommandations standards établies essentiellement chez les sujets plus jeunes. La plupart des données dérivent d’essais multicentriques ayant étendu l’age limite supérieur d’inclusion à 65 ou 70 ans. Un seul essai multicentrique, fran?ais, a spécifiquement abordéle r?le d’une chimiothérapie adjuvante à base d’anthracyclines ajoutée au tamoxifène chez le sujet de plus de 65 ans. Pourtant plusieurs revues rétrospectives de groupes coopérateurs internationaux semblent démontrer lemame béneéfice potentiel d’une chimiothérapie adjuvante chez les sujets agés que chez les sujets plus jeunes, sous réserve d’une vigilance accrue à l’égard des effets secondaires. Avec l’aide ajustée d’échelles spécifiques gériatriques, les cliniciens doivent apprendre à intégrer bénéfice absolu, espérance de vie et tolérance, trois volets essentiels pour abandonner la discrimination ancienne reposant sur l’age, inadaptée à l’évolution de nos moyens et pratiques.