Citations

Abstract Poor growth in early life is associated with numerous adverse outcomes later in life. In 123 adolescents 16–18 yr of age, the previous findings of a positive relation between size in early life and later bone mass was confirmed. These associations were mediated by the current height and weight, but it was not confirmed that alterations of the GH–IGF axis cause this. Introduction: Numerous studies have found associations between low birth weight and disease later in life, including decreased bone mass. Materials and Methods: A longitudinal cohort of 16- to 19-year-old adolescents (n = 123) with data on third trimester fetal growth velocity (FGV) was assessed by serial ultrasound measurements, birth weight (BW), and weight at 1 yr. A follow-up study included DXA scan, anthropometric measurements, and measurements of the growth hormone (GH) –IGF-I axis in a representative subpopulation (n = 30). Results: BW and weight at 1 yr were positively associated with whole body BMC (p = 0.02 and p < 0.0001, respectively), lumbar spine BMC (p = 0.001 and p = 0.03, respectively), and lumbar spine BMD (p = 0.04). After correction for adolescent height and weight, no association remained significant. There was no relation between IGF-I and IGF binding protein 3 (IGFBP-3) levels in adolescence and size in early life or bone mass. In the subpopulation, GH secretion (median, 2.58 versus 4.05), GH pulse mass (median, 10.7 versus 19.4 mU/liter), and total GH (median, 74.9 versus 108.8 mU/liter/12 h) were decreased in the small for gestational age (SGA) group compared with the appropriate for gestational age (AGA) group; this did not reach statistical significance. Likewise, there were no differences in IGF-I, IGF-II, and IGFBP-1, −2, and −3 levels between the SGA and AGA groups. A statistically significant positive association between FGV and adolescent IGF-II was found (B = 199.9, p = 0.006). Significant negative associations between GH measurement and BMC, as well as BMD, were found (B = −0.008, p = 0.005 and B = −0.008, p = 0.006, respectively). Conclusions: This study confirms the previous findings of a positive relation between size in early life and later BMC, an association apparently independent of the distal part of the GH/IGF-I axis. However, this association may be mediated mainly by postnatal growth determining size of the skeletal envelope rather than an effect of fetal programming on bone mass per se.

Migraineurs with frequent aura (≥1 per month) are at a 12-fold increased risk of posterior circulation infarctions. Although the mechanism is unclear, these lesions are located in the arterial borderzone of the cerebellum. This case illustrates, for the first time, crossed cerebellar diaschisis in a patient with migraine with prolonged aura, and raises the possibility that hypoperfusion may be responsible in part for the development of these lesions.

AbstractEmbryonic stem cells or their progeny inevitably differ genetically from those who might receive the cells as transplants. We tested the barriers to engraftment of embryonic stem cells and the mechanisms that determine those barriers. Using formation of teratomas as a measure of engraftment, we found that semiallogeneic and fully allogeneic embryonic stem cells engraft successfully in mice, provided a sufficient number of cells are delivered. Successfully engrafted cells did not generate immunological memory; unsuccessfully engrafted cells did. Embryonic stem cells reversibly, and in a dose-dependent manner, inhibited T-cell proliferation to various stimuli and the maturation of antigen-presenting cells induced by lipopolysaccharide. Inhibition of both was owed at least in part to production of transforming growth factor-β by the embryonic stem cells. Thus, murine embryonic stem cells exert “immunosuppression” locally, enabling engraftment across allogeneic barriers.Disclosure of potential conflicts of interest is found at the end of this article.

Abstract Isolated central nervous system (CNS) relapse involving the brain parenchyma is a rare complication of systemic non-Hodgkin lymphoma. We retrospectively analyzed patient characteristics, management, and outcomes of this complication. After complete response to initial non-Hodgkin lymphoma treatment, patients with isolated CNS relapse with the brain parenchyma as initial relapse site were eligible. Patients with isolated CNS relapse involving only the cerebrospinal fluid were not eligible. Information on 113 patients was assembled from 13 investigators; 94 (83%) had diffuse large B-cell lymphoma. Median time to brain relapse was 1.8 years (range, 0.25-15.9 years). Brain relapse was identified by neuroimaging in all patients; in 54 (48%), diagnostic brain tumor specimen was obtained. Median overall survival from date of brain relapse was 1.6 years (95% confidence interval, 0.9-2.6 years); 26 (23%) have survived 3 years or more. Median time to progression was 1.0 year (95% confidence interval, 0.7-1.7 years). Age less than 60 years (P = .006) at relapse and methotrexate use (P = .008) as front-line treatment for brain relapse were significantly associated with longer survival in a multivariate model. Our results suggest systemic methotrexate is the optimal treatment for isolated CNS relapse involving the brain parenchyma. Long-term survival is possible in some patients.