Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.      

Assessment of fetal behavior and general movements by four-dimensional sonography

The aim of this paper was to review the clinical applications of four-dimensional ultrasonography in the assessment of fetal behavior. With the use of a computerized database, articles on three-dimensional ultrasonography were reviewed. Several applications of dynamic three-dimensional ultrasonography have been reported, including imaging of fetal movements, facial expression and fetal hand movements. The importance of the assessment of fetal behavior by four-dimensional sonography is stressed. Four-dimensional sonography seems to be a useful imaging tool for clinical problem solving in perinatology, especially in observing the development of the central nervous system in utero.     

Is a prophylactic treatment by erythropoietin relevant to reduce red blood cell transfusion in the pediatric intensive care unit?

OBJECTIVE: An adult trial reported the efficacy of recombinant human erythropoietin in critically ill patients with a 19% decrease in red blood cell transfusion. Our aim was to evaluate the relevance of this prophylactic treatment in children hospitalized in a pediatric intensive care unit (PICU). DESIGN: Cohort study from January 1995 to December 2004. SETTING: University hospital PICU. PATIENTS: Children between 1 month and 18 yrs of age. INTERVENTIONS: We searched through a prospective databank for all children hospitalized in the PICU for > or =4 days (potential recipients of erythropoietin, as proposed in the adult trial) and transfused with red blood cells after day 7 following PICU entry (in whom erythropoietin might prevent anemia, according to results of the adult trial). MEASUREMENTS AND MAIN RESULTS: We found that 799 of 2,578 children (31%) were hospitalized for > or =4 days. The study group comprised 787 patients who were hospitalized for > or =4 days in the PICU and for whom full records were available. One hundred eighty-three children in this study group were transfused during their stay in the PICU (median age, 7 months; weight, 6.60 kg). Hemoglobin levels before transfusion (mean +/- sd) were 7.7 +/- 1.5 g/dL. These transfused children represented 23% of the study group and 7% of the total PICU admissions. Forty-seven children (6% of the study group, 2% of the total PICU admissions) were transfused with red blood cells after 7 days of hospitalization and could have benefited from a prophylactic treatment with erythropoietin. Relative risk to benefit of a prophylactic treatment by erythropoietin was higher in cases of mechanical ventilation (relative risk, 1.18) and inotropic treatment (relative risk, 1.72) and if the main diagnosis involved dermatological (relative risk, 3.03) or oncologic disease (relative risk, 3.94). CONCLUSIONS: If we applied the results of the adult trial to our PICU, we would have to treat 31% of the children with prophylactic erythropoietin and thereby expect a reduction of one red blood cell transfusion for every 17 treated patients.     

Rapid diagnosis of glucocorticoid suppressible hyperaldosteronism in infants and adolescents

Glucocorticoid suppressible hyperaldosteronism (GSH) is an uncommon form of dominantly inherited hypertension. Presentation with hypertension and complications such as stroke in early life are well recognised. The use of a simple genetic test carried out on blood or placenta facilitates the detection of infants and children with GSH before the development of hypertension, allowing prompt treatment of hypertension if it occurs, and an opportunity to study the effects of growth and environmental influences on the progression of the condition.     

Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1- antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.