Estimation of the energy cost of physical activity in infancy

OBJECTIVE: To estimate physical activity energy expenditure (AEE) in groups of free living infants in the first year of life. DESIGN: Mixed longitudinal study of 124 healthy infants, using 232 estimations of AEE made between 1.5 and 12 months. Infants studied at more than one time point were treated as new cross sectional data points. Total energy expenditure and body composition were estimated using doubly labelled water. Sleeping metabolic rate was predicted from weight. RESULTS: AEE increased from 5% of energy intake at 1.5 months to 34% at 12 months. Growth costs declined by 90%, but metabolisable intake by only 20%, over the same period. CONCLUSIONS: Energy is increasingly diverted from growth to activity during infancy. Values for AEE may aid in estimating energy requirements of groups factorially. Further work is required, however, on individual variability in AEE, and on the effects of disease, hospitalisation, surgery, and malnutrition.     

Growth and growth hormone secretion after bone marrow transplantation

This study analyses the growth and the growth hormone secretion of children given various conditioning protocols before bone marrow transplantation (BMT). Twenty nine children (14 boys, 15 girls) given BMT were classified according to their conditioning protocol: total body irradiation (TBI) given as a single exposure of 10 Grays (Gy, group I, 11 cases), or 8 Gy (group II, four cases), 12 Gy given as six fractionated doses (Group III, seven cases), or chemotherapy alone (group IV, seven cases). The arginine-insulin stimulated growth hormone peak, 2-7.5 years after BMT, was > 10 micrograms/l in all patients except four from group I (6.9-8.9 micrograms/l). A second growth hormone secretion evaluation was performed in 10 group I patients because of persistent low growth velocity despite a normal growth hormone peak. There were no significant changes in the mean (SEM) stimulated growth hormone peak (18.4 (2.2) v 20.1 (3.6) micrograms/l) at 3 (0.3) to 5.2 (0.6) years after BMT. The sleep growth hormone peaks and concentrations (n = 6) were normal. The mean cumulative height changes (SD) during the three years after BMT were: -1.4 (0.2) in group I, -0.1 (0.4) in group II, -0.4 (0.2) in group III, and 1.5 (0.5) in group IV; this was significant in groups I and IV. The final heights of two monozygotic twins (BMT donor and recipient) had differed by 17.5 cm, despite them both having normal growth hormone peaks and puberty. Eight patients, treated for congenital immune deficiency syndrome, were growth retarded at the time of BMT. Of these, only those conditioned by chemotherapy alone had significant catch up growth (2(0.6)SD) while those conditioned by a single Gy exposure did not (0(0.4)SD). It is concluded that the total radiation dose is critical for growth evolution, as is the fractionation schedule. For the TBI doses and the interval since BMT studied, there was no correlation between growth hormone peak and the height loss. The rapidity of decreased growth velocity after TBI and the comparison between the monozygotic twins suggest that radiation induced skeletal lesions are partly responsible for the decreased growth.     

Spinal abnormalities in pediatric patients: MR imaging findings compared with clinical, myelographic, and surgical findings

Eighty-one pediatric patients with a variety of spinal disorders, including suspected dysrhaphism, scoliosis, neoplasia, and neurofibromatosis, underwent magnetic resonance (MR) imaging. The results were retrospectively compared with those of myelography followed by computed tomography (CT) and surgery. In patients with dysrhaphism, most abnormalities, including hydromyelia, inclusion tumors, and sites of cord tether, were demonstrated with MR imaging. Diastematomyelia and small hydromyelic cavities were indistinguishable on routine coronal and sagittal T1-weighted images; axial images with T2 weighting were optimal for this differentiation. MR imaging did not enable direct visualization of a thickened filum or evaluation of tethering with a thin, dorsally positioned neural placode. Congenital or severe scoliosis required lengthy studies with multiple planes of imaging or myelography and CT. Milder curvatures were readily evaluated with MR imaging, and neoplastic lesions, with the exception of intrathecal tumor seeding, were adequately defined.     

HLA-B27 associated arthropathies

The association between histo-compatibility antigens and disease is reviewed, in particular that between HLA-B27 and spondylitic disorders, i.e., ankylosing spondylitis, Reiter's arthritis, psoriatic arthritis, and ankylosing hyperostosis. We determined whether the presence of HLA-B27 predicted specific radiographic findings and, conversely, whether specific radiographic changes predicted antigenic status. The prevalences of the HLA-B27 antigen in our patients were: ankylosing spondylitis, 100%; Reiter's arthritis, 93%; psoriatic arthritis, 55%; and ankylosing hyperostosis, 12%. The only specific radiographic finding associated with B27 positivity was severe spondylitis in psoriasis.     

Human, canine and murine BRCA1 genes: sequence comparison among species

Five to ten percent of breast cancer in the western world may be attributed to the inheritance of highly penetrant mutations in the breast and ovarian cancer susceptibility gene, BRCA1. The biological function of BRCA1 and factors affecting expressivity, such as gene- environment and gene-gene interactions, may be more effectively studied in appropriate animal models. We report the cloning and sequencing of the canine and murine BRCA1 genes and contrast the sequences with human BRCA1. The amino terminal 120 residues of the gene are > 80% identical among the three species. The C-terminus is also highly conserved, containing an 80 amino acid stretch that is over 80% identical. Motifs of likely functional significance are maintained, including the amino terminal RING finger motif (amino acids 24-64) and the granin consensus sequence (1214-1223). The distribution of missense mutations and neutral polymorphisms identified in BRCA1-linked breast cancer suggests that disease associated missense mutations occur at highly conserved residues whereas polymorphisms are in regions of lower conservation. Among eighteen missense mutations with unknown consequences, seven occur in amino acids that are identical across species. Four of these seven (E1219D, A1708E, P1749R and M1775R) are also within conserved domains. Taken together, these data predict regions of the gene which may be critical for normal function.      

Identifying mental health services in clinical genetic settings

The purpose of this study was to examine the mental health needs of individuals at risk for adult onset hereditary disorder (AOHD) from the perspective of their genetic service providers, as it is unknown to what extent psychosocial services are required and being met. A mail-out survey was sent to 281 providers on the membership lists of the Canadian Association of Genetic Counsellors and the Canadian College of Medical Geneticists. The survey assessed psychosocial issues that were most commonly observed by geneticists, genetic counsellors (GCs), and nurses as well as availability and types of psychosocial services offered. Of the 129 respondents, half of genetic service providers reported observing signs of depression and anxiety, while 44% noted patients' concerns regarding relationships with family and friends. In terms of providing counselling to patients, as the level of psychological risk increased, confidence in dealing with these issues decreased. In addition, significantly more GCs reported that further training in psychosocial issues would be most beneficial to them if resources were available. As a feature of patient care, it is recommended that gene-based predictive testing include an integrative model of psychosocial services as well as training for genetic service providers in specific areas of AOHD mental health.     

Angiogenèse tumorale: physiopathologie, valeur pronostique et perspectives thérapeutiques

Introduction. -- Angiogenesis activation plays a crucial role in tumoral growth and metastases dissemination. This review summarizes and analyzes current knowledge on molecular mechanisms related to angiogenesis and the prognostic value of its effectors. It also focuses on the therapeutical relevance of various drugs that might inhibit angiogenesic processes.Current knowledge and key points. -- Tumor angiogenesis involves complex interactions between tumoral, stromal, endothelial cells, fibroblasts and the extracellular matrix. Normal and malignant angiogenesis depends on the balance of proangiogenic and antiangiogenic factors. Endothelial cells are activated by growth factors, such as Vascular Endothelial Growth Factor (VEGF), and proliferate; they release proteases able to induce degradation of the basement membrane and extracellular matrix, and undergo migration and tubulogenesis. Angiostatin and endostatin are two powerful inhibitors of angiogenesis in experimental models. Assessment of intratumoral microvessel density and quantification of angiogenic factors, including VEGF, are of prognostic value in most cancers, particularly in breast cancer. However, the use of these prognosis markers in clinical practice is still controversial due to the lack of prospective studies and to technical limits inherent to the scoring and standardization of immunohistochemical methods.Future prospects and projects. -- Better understanding of the molecular basis of angiogenesis allows the development of new therapeutical strategies. Biochemical targets of antiangiogenic therapy are: the interaction between angiogenic factors and their receptors; the interaction of endothelial cells with the extracellular matrix; and intracellular signaling pathways. Angiogenesis inhibitors may not cause tumor regression, but inhibit cellular growth and produce «disease dormancy». Extensive phase I to III clinical trials involving antiangiogenesis therapy are in progress.

Résumé

Propos. -- Dans les cancers, l'activation de l'angiogenèse joue un rôle important dans le développement tumoral et dans la dissémination métastatique. L'objectif de cette revue est de faire le point sur la physiopathologie et la valeur pronostique de l'angiogenèse tumorale, et sur les perspectives thérapeutiques visant à l'inhiber.Actualités et points forts. -- L'angiogenèse tumorale se met en place grâce à des interactions cellulaires et moléculaires complexes entre cellules cancéreuses, cellules endothéliales, cellules du stroma tumoral et les constituants de la matrice extracellulaire. La croissance et la dissémination des tumeurs solides malignes dépendent d'un équilibre existant entre régulateurs positifs et négatifs de l'angiogenèse tumorale. Les cellules endothéliales peuvent, grâce à l'action de facteurs de croissance sécrétés par les cellules cancéreuses eg vascular endothelial growth factor (VEGF), entrer dans le cycle cellulaire, migrer après rupture de la membrane basale et s'organiser spatialement, pour former les vaisseaux irriguant la tumeur. L'angiostatine et l'endostatine, sont deux puissants inhibiteurs de l'angiogenèse dans des modèles de carcinogenèse expérimentale. De nombreuses études rétrospectives, portant le plus souvent sur la densité en microvaisseaux et plus rarement sur le VEGF, ont montré dans de nombreux cancers et en particulier le cancer du sein, une association entre angiogenèse et pronostic. Cependant, l'intérêt en clinique de ces facteurs pronostiques est controversé en raison du manque d'études prospectives et des limitations inhérentes à la quantification et à la standardisation des études immunohistochimiques.Perspectives et projets. -- Une meilleure compréhension des processus moléculaires et physiopathologiques activant l'angiogenèse tumorale permet d'élaborer de nouvelles approches thérapeutiques. Actuellement, les inhibiteurs de l'angiogenèse visent trois cibles moléculaires : la liaison des facteurs angiogéniques aux récepteurs, l'interaction entre les cellules endothéliales et la matrice extracellulaire et la transmission intracellulaire du signal. Les thérapeutiques anti-angiogéniques sont en cours d'évaluation dans des études de phase I à III.