Immune cell counts and risks of respiratory infections among infants exposed pre- and postnatally to organochlorine compounds: a prospective study

<p>Abstract</p> <p>Background</p> <p>Early-life chemical exposure may influence immune system development, subsequently affecting child health. We investigated immunomodulatory potentials of polychlorinated biphenyls (PCBs) and <it>p,p'</it>-DDE in infants.</p> <p>Methods</p> <p>Prenatal exposure to PCBs and <it>p,p'</it>-DDE was estimated from maternal serum concentrations during pregnancy. Postnatal exposure was calculated from concentrations of the compounds in mother's milk, total number of nursing days, and percentage of full nursing each week during the 3 month nursing period. Number and types of infections among infants were registered by the mothers (N = 190). White blood cell counts (N = 86) and lymphocyte subsets (N = 52) were analyzed in a subgroup of infants at 3 months of age.</p> <p>Results</p> <p>Infants with the highest prenatal exposure to PCB congeners CB-28, CB-52 and CB-101 had an increased risk of respiratory infection during the study period. In contrast, the infection odds ratios (ORs) were highest among infants with the lowest prenatal mono-<it>ortho </it>PCB (CB-105, CB-118, CB-156, CB-167) and di-<it>ortho </it>PCB (CB-138, CB-153, CB-180) exposure, and postnatal mono- and di-<it>ortho </it>PCB, and <it>p,p'</it>-DDE exposure. Similar results were found for pre- and postnatal CB-153 exposure, a good marker for total PCB exposure. Altogether, a negative relationship was indicated between infections and total organochlorine compound exposure during the whole pre- and postnatal period. Prenatal exposure to CB-28, CB-52 and CB-101 was positively associated with numbers of lymphocytes and monocytes in infants 3 months after delivery. Prenatal exposure to <it>p,p'</it>-DDE was negatively associated with the percentage of eosinophils. No significant associations were found between PCB and <it>p,p'</it>-DDE exposure and numbers/percentages of lymphocyte subsets, after adjustment for potential confounders.</p> <p>Conclusion</p> <p>This hypothesis generating study suggests that background exposure to PCBs and <it>p,p'</it>-DDE early in life modulate immune system development. Strong correlations between mono- and di-<it>ortho </it>PCBs, and <it>p,p'</it>-DDE exposures make it difficult to identify the most important contributor to the suggested immunomodulation, and to separate effects due to pre- and postnatal exposure. The suggested PCB and <it>p,p'</it>-DDE modulation of infection risks may have consequences for the health development during childhood, since respiratory infections early in life may be risk factors for asthma and middle ear infections.</p

High-Dose Chemotherapy Followed by Autologous Stem Cell Transplantation for Metastatic Rhabdomyosarcoma—A Systematic Review

INTRODUCTION: Patients with metastatic rhabdomyosarcoma (RMS) have a poor prognosis. The aim of this systematic review is to investigate whether high-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (HSCT) in patients with metastatic RMS has additional benefit or harm compared to standard chemotherapy. METHODS: Systematic literature searches were performed in MEDLINE, EMBASE, and The Cochrane Library. All databases were searched from inception to February 2010. PubMed was searched in June 2010 for a last update. In addition to randomized and non-randomized controlled trials, case series and case reports were included to complement results from scant data. The primary outcome was overall survival. A meta-analysis was performed using the hazard ratio as primary effect measure, which was estimated from Cox proportional hazard models or from summary statistics of Kaplan Meier product-limit estimations. RESULTS: A total of 40 studies with 287 transplant patients with metastatic RMS (age range 0 to 32 years) were included in the assessment. We identified 3 non-randomized controlled trials. The 3-year overall survival ranged from 22% to 53% in the transplant groups vs. 18% to 55% in the control groups. Meta-analysis on overall survival in controlled trials showed no difference between treatments. Result of meta-analysis of pooled individual survival data of case series and case reports, and results from uncontrolled studies with aggregate data were in the range of those from controlled data. The risk of bias was high in all studies due to methodological flaws. CONCLUSIONS: HDCT followed by autologous HSCT in patients with RMS remains an experimental treatment. At present, it does not appear justifiable to use this treatment except in appropriately designed controlled trials

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

Test-retest reliability of hand-held dynamometry and functional tests in systemic lupus erythematosus

The aim of this study was to evaluate the test-retest reliability and determine the degree of measurement error of tests of isometric muscle strength and upper and lower limb function in women with systemic lupus erythematosus (SLE). Twelve women with SLE (age 39.8?῱0?years) were assessed on two occasions separated by a 7-10-day interval. Strength of six muscle groups was measured using a hand-held dynamometer; function was measured by the 30-s sit to stand test and the 30-s 1?kg arm lift. Relative reliability was estimated using the intraclass correlation coefficient (ICC), model 2,1 (ICC2,1). Absolute reliability was estimated using standard error measurement and the minimal detectable difference was calculated. All ICCs were greater than 0.87. Muscle strength would need to increase by between 18% and 39% in women with SLE to be 95% confident of detecting real changes. The functional tests demonstrated a systematic bias between trials. This study demonstrates that hand-held dynamometry in SLE can be performed with excellent reliability. Further work needs to be completed to determine the number of trials necessary for both the 30-s sit to stand and 30-s 1?kg arm lift to decrease the systematic bias.No Full Tex