Is Acute Myeloblastic Leukemia in Children Under 2 Years of Age a Specific Entity? A Report from the FRENCH ELAM02 Study Group.

The clinical and biological characteristics of children under 2 years (infants) with acute myeloid leukemia (AML) are different from those of older children. We aimed to describe the specific characteristics of this population and the potential factors that influence the prognosis. We analyzed data concerning 438 children with newly-diagnosed AML treated in the ELAM02 protocol between March 2005 and December 2011, of which 103 were under 2 years old at diagnosis. The evaluation criteria were overall survival (OS) and event-free survival (EFS) of infants vs older children. The clinical and biological features were secondary criteria. Infants presented more frequent extra-medullary presentation than older children. They had a significantly higher proportion of skin lesions and central nervous system involvement (15% vs 3%, p < 0.0001 and 26% vs 12%, p = 0.0005, respectively). The global incidence of KMT2A rearrangements was nearly 55% for infants vs 11% for older children (p < 0.0001). Median 5-year OS was 70.4% for infants vs 71.4% for older children (p = 0.83). Five-year EFS was 67% for infants vs 58% for older children (p = 0.27). Infants with AML represent a cohort of patients with specific clinical and biological features. These remarkable differences had no significant impact on their outcome in the ELAM02 protocol.

[Cerebral vasculopathy in children with sickle cell disease: Key issues and the latest data]. / Vasculopathie cérébrale de l'enfant drépanocytaire : points clés et nouveautés.

Cerebral vasculopathy is a common and severe complication of sickle cell disease in children. The pathophysiology consists of progressive damage to the basal intracranial arteries and cerebral microcirculation, while chronic anemia worsens exposure to cerebral hypoxia. It results in stroke and subclinical or poorly symptomatic ischemic lesions. Many clinical, biological, and radiological risk factors have been identified. The prevention strategy through systematic transcranial Doppler screening of large-vessel vasculopathy has revolutionized the management of this disease and has greatly decreased the risk of developing stroke. MRI-MRA is a complementary diagnostic tool for anatomical analysis of parenchymal and vascular lesions, which is used for chronic disease monitoring or in the context of an acute neurological event. New exploration opportunities are offered by submandibular Doppler sonography and indirect evaluation methods of cerebral oxygenation and perfusion. If chronic blood transfusion therapy is used to prevent the occurrence and recurrence of cerebral complications of sickle cell disease, only allogeneic hematopoietic stem cell transplantation can safely and definitively stop the transfusion program. It should therefore be proposed early, before irreversible cerebral or vascular lesions occur. Hydroxycarbamide treatment has recently emerged as a potential substitute for chronic transfusions for the maintenance of transcranial Doppler velocities, but only after an initial treatment by transfusions and provided there is close follow-up. In the long run, cerebral vascular damage can cause progressive cognitive impairment and disability, even in children without radiologically identified lesions, indicating the importance of systematic and repeated neuropsychological testing.

[Incidence and prognostic factors of breast cancer diagnosed within and outside of the organised screening program in the department of Loire-Atlantique (1991-2002)]. / Incidence et facteurs pronostiques des cancers du sein découverts au cours et en dehors du programme de dépistage organisé en Loire-Atlantique (1991-2002).

BACKGROUND: This study aimed to evaluate the impact of breast cancer mass screening, which began in 1996 in Loire-Atlantique (France), on the evolution of incidence and characteristics of breast cancer between 1991 and 2002. METHODS: The cancer Registry of Loire-Atlantique recorded characteristics of 9263 incident breast cancers diagnosed between 1991 and 2002. The level of participation to the organised screening program was 48%, thus the screening management structure allowed characterizing 736 cancers discovered by organised screening between 1997 and 2002. RESULTS: The 1991-2002 period was marked by a strong increase of in situ cancer proportion (from 5% at the beginning to 10% at the end of the period) and of standardised incidence rates (from 77 to 103/10(5) and from 4 to 13/10(5) for invasive and in situ cancers, respectively). Incidence was already rising before the beginning of the organised screening program in 1996. During the 1997-2002 period, in spite of steady rates for cancers detected by organised screening, incidence of cancers detected outside organised screening went on increasing. Cancers detected by organised screening were more often of smaller size (33% versus 22% smaller than 10mm) and without lymph node invasion (70% versus 62%). CONCLUSION: A strong increase of breast cancer incidence was observed in Loire-Atlantique, particularly in the organised screening age groups. The persistent increase of in situ cancers for women younger than 50 years old unconcerned by the organised screening program, and also for women of 50-74 years old detected outside the organised screening program suggested a parallel contribution of individual screening. These preliminary results confirm better prognostic factors for cancer detected by organised screening than for others.

Social determinants of access to reference care centres for patients with colorectal cancer--a multilevel analysis.

BACKGROUND: Although social disparities in survival for patients with cancer are documented in an increasing number of papers, knowledge on the underlying mechanisms concerning screening, diagnosis, treatment or follow-up, is relatively poor. Our study was aimed at investigating the social determinants of access to reference cancer care centres for surgery for colorectal cancer in France. METHODS: Retrospective analysis was conducted on population-based data from a specialised cancer registry (County of Calvados, France). The population consisted of 5156 patients with surgical treatment for colorectal cancer recorded between January 1st 1981 and December 31st 2000. RESULTS: The probability of being cared for in a reference care centre was 1.3-fold lower for people living in a deprived district (mean income < 15000 euros) and 3-fold lower for people living in a district where more than 7% of houses were devoid of bath and shower in comparison with districts where this rate was under 2%. After adjustment for distance from reference care centre, the probability of being cared for in a reference care centre was still over one third lower for people living in a district with more than 7% of houses devoid of bath and shower. Social disparities in management of patients with colorectal cancer have increased in the last decade. The reduction of access to reference care with distance was stronger in elderly patients. CONCLUSIONS: There is a social and geographical determination of type of treatment centre for care management of colorectal cancer in France. Special attention needs to be paid to the high quality of care management in non-specialised care centres in order to avoid an increased social gradient in cancer mortality in France.

Foraging methods can affect patch choice: an experimental study in Mallard (Anas platyrhynchos).

Animals can adapt to changes in feeding conditions by switching between foraging methods. Dabbling ducks use different foraging methods, including dabbling in deep water with the head and neck submerged, and grubbing in the mud (or shallow water) where the eyes are above the surface, so the bird can visually monitor its environment while foraging. Deep foraging is considered to provide lower intake rates and to have high associated costs, such as predation risk, compared to shallow foraging. Ducks should thus prefer shallow foraging and switch to deeper methods when feeding conditions deteriorate. We conducted a set of experiments with Mallard to assess the importance of intake rate as a cue to choose between patches associated with different foraging methods, and evaluate the influence of food depletion on the decision to switch between methods. When 50 g of wheat were presented in two patches, one at a depth of 5 cm and one at 35 cm, most of the foraging was in the shallow area. Reducing food abundance to 10 g in the shallow area led to an increase in deep foraging, although the birds still preferred the shallow area at the beginning of the tests despite the fact that it did not provide a higher intake rate. This area was used until complete depletion, and birds did not turn to deep foraging before ensuring that the shallow patch was empty. These results show that food depletion affects the choice between feeding patches hence foraging method. However the value of intake rate is not the main cue for decision, rather the birds appear to choose between patches with different methods on account of their respective costs.

Nitric oxide production during endotoxin-induced mastitis in the cow.

Nitric oxide production was measured during endotoxin-induced mastitis. One hour after morning milking, the right hind quarters of 15 cows were infused with saline containing Escherichia coli endotoxin. Left hind control quarters were infused with saline only. At varying intervals before and after infusion, diagnostic markers of mastitis were recorded and nitric oxide production was evaluated by measuring nitrite plus nitrate levels in milk. In endotoxin-infused quarters, a significant increase in nitrite plus nitrate concentrations was observed 3 h postinfusion; concentrations decreased to preinfusion levels within 48 h. This change indicates that significant amounts of nitric oxide are released during endotoxin-induced mastitis. At 3 different time points, somatic cells were harvested from milk samples, plated, and maintained in culture for 24 h. The concentration of nitrite plus nitrate in medium from cells harvested 12 h postinfusion was increased, suggesting that nitric oxide is released, at least in part, by milk somatic cells. In a second set of experiments, we evaluated nitric oxide production when animals were infused with endotoxin and aminoguanidine, a specific inhibitor of the inducible form of nitric oxide synthase. In cows treated with aminoguanidine, the increase in nitrite plus nitrate observed after endotoxin infusion was prevented. These results suggest that nitric oxide production during endotoxin-induced mastitis resulted from the activity of the inducible form of nitric oxide synthase. They also support a possible involvement for nitric oxide in the inflammatory reaction observed during mastitis.

Regulation of CCAAT/enhancer binding protein isoforms by serum and glucocorticoids in the rat intestinal epithelial crypt cell line IEC-6.

Members of the CCAAT/enhancer binding protein (C/EBP) gene family are expressed in murine intestine. However, little is known about their regulation in intestinal epithelial cells. In an attempt to determine regulatory mechanisms involved in their expression, we examined C/EBP alpha, beta, and delta isoform expression in response to serum and glucocorticoids in the rat intestinal epithelial crypt-derived cell line IEC-6, by Northern blot, transcription run-on assays, indirect immunofluorescence, Western blot, and electrophoretic mobility shift assays. Serum leads to rapid and transient increases in C/EBP alpha and beta mRNA and protein levels by posttranscriptional regulatory mechanisms, without affecting transcriptional initiation. However, C/EBP-specific DNA binding capacity is not affected by serum. Whereas C/EBP alpha expression is not regulated by glucocorticoids, C/EBP beta and delta mRNA and protein levels are rapidly induced. These inductions result from both increased transcription rates and posttranscriptional regulatory mechanisms as well. Moreover, C/EBP beta and delta containing DNA binding complexes are increased by glucocorticoids as determined by supershift assays, in contrast to C/EBP alpha containing complexes. Immunofluorescence studies show cytoplasmic and nuclear localization for C/EBP alpha, in contrast to a restricted nuclear localization for both C/EBP beta and C/EBP delta. These results confirm C/EBP isoforms expression in intestinal epithelial cells. Differential regulation by serum and glucocorticoids as well as different localization of three C/EBP isoforms suggest a role for this class of transcription factors in the control of gene expression in intestinal epithelial cells.

Differential expression of fos and jun family members during murine postnatal intestinal development.

We have examined the patterns of expression of members of the fos and jun families of transcription factors during murine postnatal intestinal development. Northern analysis showed increases in fosB, c-fos, and junB mRNA levels in both proximal jejunum and colon. These increases coincide with weaning a period of major changes in intestinal cell proliferation and migration. Administration of dexamethasone to suckling mice resulted in transient induction of c-fos mRNA levels in all gut segments. Thus, modifications in expression of certain members of the fos and jun families in vivo correlate with major maturational changes during murine intestinal development and support a role for these transcription factors in the regulation of intestinal functions.

CCAAT/enhancer binding protein isoforms expression in the colon of neonatal mice.

Development of murine proximal colon follows a complex pattern of morphological and functional differentiation. Molecular mechanisms and factors responsible for colon-specific gene expression remain to be established. In an attempt to identify some of these factors, we examined the expression of the alpha, beta, and delta isoforms of the CCAAT/enhancer binding protein (C/EBP) transcription factor gene family during murine colon development. Whereas C/EBP alpha mRNA levels are reduced during the third post-natal week, C/EBP alpha 42 and 30 kD proteins levels decrease between post-natal days 8 and 21. C/EBP beta mRNA levels increase between post-natal days 4 and 8 and remain constant subsequently, in contrast to a decrease in C/EBP beta protein levels between post-natal days 11 and 15. C/EBP delta mRNA levels increase gradually while C/EBP delta protein levels show variations during post-natal development. Changes in C/EBP DNA binding activity coincides with modifications in C/EBP isoforms expression. By indirect immunofluorescence, we show restriction of C/EBP alpha expression to differentiated surface epithelial cells during crypt formation. C/EBP alpha is predominantly nuclear with some cytoplasmic staining at all developmental stages. C/EBP beta and delta are both predominantly nuclear in crypt and differentiated surface epithelial cells, as well as in various cells of the lamina propria and muscular layers. Thus, specific C/EBP isoforms are differentially regulated during murine colon post-natal development. Differential C/EBP isoforms pattern of expression suggests a role for these transcription factors in colon-specific gene expression during development.

Determination of the intrinsic Michaelis constant of immobilized alpha-chymotrypsin.

The Michaelis constant of alpha-chymotrypsin, immobilized on a glutaraldehyde-activated silicate support, for N-glutaryl-L-phenylalanine-p-nitroanilide was determined and was found to be identical with that of the enzyme in solution. The influence of intraparticular diffusion was taken into account by immobilizing different amounts of enzyme, thus changing the magnitude of diffusional constraints and extrapolating apparent Michaelis constants, determined for each amount of immobilized enzyme, to zero diffusional constraints. The possible effect of the immobilized enzyme distribution inside the porous matrix was investigated through numerical simulations.

[The young homeless of Montreal: a longitudinal study]. / Les jeunes itinérants de Montréal: une enquête transversale.

A transverse survey conducted in 142 young homeless (age: 18-30) shows that they mainly come from broken families where alcoholism, violence and mental illness hold an important place. Regarding work, the majority of the surveyed homeless have not worked more than 24 months in all their life and have nearly continuously been on welfare; those who had jobs lost them much more because of their alcohol or drug use and their problems of interpersonal relationships than because of unemployment. On a personal level, these young adults are particularly battling against two major problems: alcoholism and drug addiction, and mental illness. Although 23% of the surveyed subjects have already been hospitalized in psychiatry, the majority of these young homeless have never received any psychiatric care. Nevertheless, they show mental health problems which are often mistakenly dismissed as the effects of alcoholism or chronic drug abuse. The authors believe that means of detection and adequate treatment must be developed for this growing population instead of thinking of social measures which would only give the young homeless a meal and protection from the elements.