Can ‘personalized diagnostics’ promote earlier intervention for dysglycaemia? Hypothesis ready for testing

The risk associated with progression to diabetes as well as for cardiovascular complications increases along a continuum, rather than being threshold‐dependent. How can we identify those with glucose levels in the upper reaches of normal who are most in need of a preventive intervention? With present criteria, we are likely excluding many individuals who have heightened risk. We introduce here the possibility of using a “personalized” glucose profile to encourage early intervention in subjects in whom glucose metabolism is deteriorating (on an individual level) but not yet abnormal on a population‐based norm. We further suggest that “personalized profiles” of hemoglobin A1c and basal plasma insulin may also help encourage appropriately early intervention. That the first line therapies are so effective, safe and simple make these more sensitive approaches very attractive. Copyright © 2010 John Wiley & Sons, Ltd.     

Perceived social support predicts self-reported and objective health and health behaviors among pregnant women

Perinatal health and health behaviors play a crucial role in maternal and neonatal health. Data examining psychosocial factors which predict self-reported health and health behaviors as well as objective indicators downstream of health behaviors among pregnant women are lacking. In this longitudinal study design with 131 pregnant women, perceived social support was examined as a predictor of self-rated health and average levels of sleep quality, health-promoting and health-impairing behaviors, and red blood cell (RBC) polyunsaturated fatty acids across early, mid, and late pregnancy. Participants provided a blood sample and fatty acid methyl esters were analyzed by gas chromatography. Measures included the Multidimensional Scale of Perceived Social Support, Pittsburgh Sleep Quality Index, and Prenatal Health Behavior Scale. Regression models demonstrated that, after adjustment for income, race/ethnicity, age, relationship status, pre-pregnancy body mass index, greater social support was associated with better self-rated health (p?=?0.001), greater sleep quality (p?=?0.001), fewer health-impairing behaviors (p?=?0.02), and higher RBC omega-3 fatty acids (p?=?0.003). Associations among social support with health-promoting behaviors, RBC omega-6 fatty acids, or gestational weight gain were not significant. Findings underscore the benefits of perceived social support in the context of pregnancy. Examination of pathways that link social support with these outcomes will be meaningful in determining the ways in which perinatal psychosocial interventions may promote health.

     

Double-Negative T Cell Levels Correlate with Chronic Graft-versus-Host Disease Severity

Chronic graft-versus-host disease (cGVHD) is a major complication, affecting 50% to 80% of long-term survivors of allogeneic hematopoietic stem cell transplantation. Current cGVHD therapies are neither specific nor curative, and patients are typically maintained for several months to years under immunosuppressive regimens that are associated with important side effects and increased susceptibility to life-threatening infections. As a result, continued investigation into the pathology of the disease and the search for novel diagnostic and therapeutic strategies to treat cGVHD remains a high priority. We report that the cellular dynamics of various immune cell subsets are related to cGVHD onset and severity in a cohort of allogeneic hematopoietic stem cell transplantation recipients. We document a decrease in the proportion of CD45RO⁺ CD4^?CD8^? (double-negative [DN]) T cells at the onset of cGVHD, a time at which serum levels of B cell activating factor and B cells are increased. We also find that DN T cell levels are correlated with cGVHD severity. Our present findings are in line with the view that activated DN T cells exhibit their immunoregulatory potential by eliminating B cells in vivo. Taken together, these findings suggest that maintaining elevated DN T cell numbers before the onset of cGVHD may prevent pathological B cell responses.     

Regression of juvenile idiopathic scoliosis

For a young scoliotic boy the customary "wait and watch" management program for rapidly progressive juvenile idiopathic scoliosis was considered unsatisfactory in view of the poor prognosis. The management program devised was based on the congenital postural induction concept of scoliosis with progression accruing from mechanically induced bioengineering fatigue, cumulative molecular scissions, laxity of ligaments, and secondary bone deformation. A coexisting pelvic tilt with restricted movement of the hip and shoulder joints was overlooked initially. Possibly induced simultaneously with the scoliosis, it is considered a contributory factor in scoliosis progression and requires early diagnosis and correction. The rapid improvement in this child's spinal status achieved by physiological traction and specifically designed exercises was such that as a preventive measure the technique warrants further clinical assessment on young scoliotics.     

Infliximab‐related weight gain in inflammatory bowel disease: associations and financial impacts

Association between tumour necrosis alpha inhibitors and weight gain has been reported. We examined weight change in our cohort of inflammatory bowel disease patients treated with infliximab (IFX) for over 12 months, its associations and financial implications. Two‐thirds of patients gained weight during the course of therapy. The mean change in weight after 12 months of IFX therapy was 3.3 (±6.5) kg.     

Transfer of L-alpha-acetylmethadol (LAAM) and L-alpha-acetyl-N-normethadol (norLAAM) by the perfused human placental lobule

The agonists buprenorphine and l-alpha-acetylmethadol (LAAM) were introduced as alternatives to methadone for treatment of the adult opiate addict. The direct and indirect effects of these drugs on normal fetal growth and development are currently under investigation in our laboratory. The goal of this report is to provide part of the data necessary to assess the safety of LAAM in treatment of the pregnant opiate addict. To achieve this goal, the technique of dual perfusion of placental lobule was utilized to determine the kinetics for transplacental transfer of LAAM and its effects on the viability and functional parameters of the tissue. LAAM is rapidly metabolized to the pharmacologically active norLAAM that was also included in this investigation. The two opiates were transfused at their plasma levels in patients under treatment, a concentration of 35 ng/ml. The drugs exhibited similar pharmacokinetic profiles, characterized by an initial phase of distribution into placental tissue followed by their low transfer to the fetal circuit. During the 4-h experimental period, the transfused tissue retained significant amounts of LAAM and norLAAM, and neither drug was metabolized. LAAM did not affect placental tissue viability and functional parameters. However, norLAAM caused a significant decrease in the release of human chorionic gonadotropin. At this time, it is unclear whether a similar effect for norLAAM may occur in vivo and, if so, what the consequences would be on its role in implantation and normal fetal growth and development.     

Multiple cutaneous leiomyomas leading to discovery of novel splice mutation in the fumarate hydratase gene associated with HLRCC

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant condition, which manifests as cutaneous leiomyomas (CL), uterine fibroids and renal cell cancer (RCC). We describe the case of a 53‐year‐old woman who presented with multiple CL with a novel heterozygous canonical splice site mutation in intron 9 of the fumarate hydratase (FH) gene IVS 9–1 G>C ( NM_000143.3 :c 1391–1 G>C) that was not detected on initial screening of a mutation hotspot but was picked up on sequencing the remaining exons and splice site junctions. This report highlights the importance of clinical suspicion in the diagnosis of HLRCC in the absence of a family or personal history of cancer and despite initial genetic testing being negative.