Assessment of nutritional status in children with cystic fibrosis: conventional anthropometry and bioelectrical impedance analysis. A cross-sectional study in Dutch patients

BACKGROUND: Assessment of nutritional status in children with cystic fibrosis (CF) is clinically relevant. Methods to measure nutritional status should be reliable and non-invasive, and reference values should be available. AIM: To compare weight and height measurements and measurements of specific body compartments in children with CF. METHODS: In a cross-sectional survey of 58 children with CF (28 females), we compared height and weight (expressed as: weight-for-height, body mass index (BMI), height-for-age and weight-for-age) with fat mass (skinfold sum (SFS)), muscle mass (upper arm circumference (UAC)) and bioelectrical impedance analysis (BIA). Results were expressed as Z-scores, using Dutch reference values. RESULTS: BMI and weight-for-height were within the normal range (mean Z-score (range): -0.13 (-1.5, 2.7) and -0.02 (-1.7, 2.8)). Weight and height corrected for age were below normal (mean Z-score (range): -0.79 (-2.4, -0.05) and -1.2 (-2.8, 1.4) (P<0.01)). Lean body mass by skinfold sum (LBM(sfs)), UAC and BIA were also significantly below reference values (mean Z-score (range): -0.9 (-2.2, 1.8), -0.95 (-2.4, 1.8) and -1.1 (-3.6, 1.0) (P<0.01)). Lean body mass (LBM) by BIA correlated with LBM(sfs). BIA systematically underestimated LBM in both CF patients and in control subjects. CONCLUSION: Nutritional status of children with CF must be evaluated, using age-corrected weight and height expressed in Z-score. LBM estimated by SFS, UAC and by BIA appear to be useful, although longitudinal studies in CF children should be performed to evaluate their clinical significance in detecting changes in nutritional status.     

Are cytokines possible mediators of cancer cachexia?

The possible role of cytokines in the development of cancer cachexia was reviewed from the literature. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, interferon (IFN)-gamma and leukemia inhibitory factor (LIF) can elicit many but not all host changes seen in cancer cachexia, including loss of appetite, loss of body weight, and the induction of acute-phase protein synthesis. However, these cytokines are not always demonstrated in the circulation of the cancer patients. The inability to detect circulating cytokines may be due to their low rate of production, their short half-life and rapid clearance from plasma, or their mode of action (autocrine or paracrine). Different cytokines are induced to stimulate the same response. This is very different from hormonal regulation, where a hormone acts on a cell directly through a specific receptor without depending on other mediators. Specific antibodies including anti-IFN-gamma, anti-TNF and anti-IL-6 antibodies, as well as the cyclooxygenase inhibitor indomethacin, have been used to reverse cancer cachexia. Overlapping physiologic activities make it unlikely that a single substance is the sole cause of cancer cachexia. It is hoped that further investigation on other cytokines and their possible relationships with hormones will help to clarify the mechanisms of cancer cachexia in the near future.This work was supported by a grant from the Japan-Sweden Foundation in 1991.     

Degree of Somatoform and Psychological Dissociation in Dissociative Disorder Is Correlated with Reported Trauma

In this study, the prevalence and severity of traumatic experiences as reported by patients with dissociative disorders and with other DSM-IV psychiatric diagnoses were compared. Furthermore, the predictive value of emotional, physical, and sexual trauma with respect to somatoform and psychological dissociation was analyzed. In contrast with comparison patients, dissociative disorder patients reported severe and multifaceted traumatization. Physical and sexual trauma predicted somatoform dissociation, sexual trauma predicted psychological dissociation as well. According to the memories of the dissociative disorder patients, this abuse occurred in an emotionally neglectful and abusive social context. Pathological dissociation was best predicted by early onset of reported intense, chronic and multiple traumatization. Methodological limitations restricting causal inferences between reported trauma and dissociation are discussed.     

Effect of a CCR5 inhibitor on viral loads in macaques dual-infected with R5 and X4 primate immunodeficiency viruses

Human immunodeficiency virus type 1 (HIV-1) fusion with its target cells is initiated by sequential interactions between its envelope glycoprotein, CD4, and a co-receptor, usually CCR5 or CXCR4. Small molecules that bind to CCR5 and prevent its use by R5 HIV-1 strains are now being developed clinically as antiviral drugs. To test whether a block to CCR5 promotes the replication of viruses that enter cells via CXCR4 and are associated with accelerated disease progression, we administered a small molecule CCR5 inhibitor, CMPD 167, to three macaques dual-infected with both R5 (SIVmac251) and X4 (SHIV-89.6P) viruses. CMPD 167 caused a rapid and substantial (on average, 50-fold) suppression of R5 virus replication in each animal. In two of the animals, but not in the third, a rapid, transient, 8- to 15-fold increase in the amount of plasma X4 virus occurred. In neither animal was the increase in X4 viral load sustained throughout therapy, however. These observations may have relevance for the development of CCR5 inhibitors for treatment of HIV-1 infection of humans.     

Anatomical parameters of cardiopulmonary system in three different lines of chickens: further evidence for involvement in ascites syndrome.

The present study was designed to compare the anatomical parameters of the cardiopulmonary system in three different lines of chickens with different susceptibility to ascites syndrome. Eggs from three different genetic lines-commercial broiler and layer lines and one native to Iran--were incubated and hatched, and 1-day-old chicks used. The relative heart and lung weights, the volumes of the heart, lung and thorax cavity, the incidence of ascites, and the related physiological parameters in these chickens were followed. Lung weight as a percentage of body weight, the relative lung and heart volume, and the volumes of the thorax cavity, before and after removing heart and lung tissues, were lower in fast-growing broiler chickens compared with the layer and native chickens. Additionally, most of these parameters (e.g. relative lung weight, lung volume and thorax cavity) were significantly decreased with age in broiler chickens but were increased in layer and native chickens, which was concomitant with the incidence of ascites in broiler chickens. Our data indicate that all cardiopulmonary parameters investigated are extremely unfavourable to broiler chickens and suggest a reduction in gas exchange area in broilers, and therefore higher susceptibility to pulmonary hypertension and ascites.     

Multiple dimensions of familial psychopathology affect risk of mood disorder in children of bipolar parents.

The aim of our study was to determine whether familial loading of unipolar disorder, bipolar disorder, and substance use disorder are associated with DSM-IV mood disorders in adolescents at risk for bipolar disorder. One hundred and forty adolescents aged 12-21 years of 86 bipolar parents participated in the study. Lifetime DSM-IV diagnoses of the bipolar offspring were assessed with the Schedule for Affective Disorders and Schizophrenia for School Age Children Kiddie-SADS-Present and Lifetime Version (SADS-PL). Parents were interviewed using the Family History Research Diagnostic Criteria (FH-RDC) which were used to calculate a continuous familial loading score (FL) for unipolar disorder, bipolar disorder, and for substance use disorder in first- and second-degree relatives of the adolescents. FL for unipolar disorder and substance use disorder were strong and independent predictors for lifetime mood disorders in the adolescents. The gender adjusted hazard ratios for mood disorders in the children were 1.5 (95% confidence interval (CI) = 1.2-2.0) for FL of unipolar disorder and 1.8 (95% CI = 1.3-2.4) for FL of substance use disorder. Expression of mood disorders in children of bipolar parents varies with the degree of additional FL of unipolar disorder and substance use disorder in the extended family.     

Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier

A human tumor xenograft (L56Br-X1) was established from a breast cancer axillary lymph node metastasis of a 53-year-old woman with a BRCA1 germ-line nonsense mutation (1806C>T; Q563X), and a cell line (L56Br-C1) was subsequently derived from the xenograft. The xenograft carries only the mutant BRCA1 allele and expresses mutant BRCA1 mRNA but no BRCA1 protein as determined by immunoprecipitation or Western blotting. The primary tumor, lymph node metastasis, and xenograft were hypodiploid by DNA flow cytometry, whereas the cell line displayed an aneuploidy apparently developed via polyploidization. Cytogenetic analysis, spectral karyotyping, and comparative genomic hybridization of the cell line revealed a highly complex karyotype with numerous unbalanced translocations. The xenograft and cell line had retained a somatic TP53 missense mutation (S215I) originating from the primary tumors, as well as a lack of immunohistochemically detectable expression of steroid hormone receptors, epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER-2), and keratin 8. Global gene expression analysis by cDNA microarrays supported a correlation between the expression profiles of the primary tumor, lymph node metastasis, xenograft, and cell line. We conclude that L56Br-X1 and L56Br-C1 are useful model systems for studies of the pathogenesis and new therapeutic modalities of BRCA1-induced human breast cancer.     

Clara cell secretory protein deficiency alters clara cell secretory apparatus and the protein composition of airway lining fluid

Clara cells represent the predominant secretory cell within distal conducting airways of mammals and exhibit functional alterations with chronic lung disease. We previously demonstrated that Clara cell secretory protein (CCSP) deficiency results in enhanced susceptibility to environmental agents. The present study was undertaken to define changes in Clara cell secretory function associated with CCSP deficiency in knockout mice. Comparative morphometry of Clara cell ultrastructure revealed dramatic alterations in secretory apparatus between wild-type (WT) and CCSP knockout (CCSP-/-) mice. Secretory granules, which occupy greater than 2% of Clara cell cytoplasmic volume in WT mice, were completely absent among Clara cells of CCSP-/- mice. Moreover, Clara cells of CCSP-/- mice exhibited a > 95% reduction in rough endoplasmic reticulum and alterations to Golgi apparatus, relative to WT controls. Ultrastructural perturbations to Clara cells were associated with altered protein composition of airway lining fluid as revealed by two-dimensional gel analysis of bronchoalveolar lavage proteins, but were not associated with altered abundance or secretion of CC26, another Clara cell secretory protein. We conclude that CCSP is required for the appearance of Clara cell secretory granules and that functional changes to Clara cells that result from CCSP deficiency lead to alterations in the composition of epithelial lining fluid.