Publications

OBJECTIVE

To evaluate the relationship between serum insulin-like growth factor 1 (IGF-1), IGF-1 binding protein 1 (IGFBP-1), and IGF-1 binding protein 2 (IGFBP-2) and fasting insulin, fasting glucose, adiposity, and mortality in older adults.

DESIGN

A prospective cohort study with mean follow-up of 6.2 years.

SETTING

Participants were recruited and followed at two centers affiliated with academic medical institutions.

PARTICIPANTS

Six hundred twenty-five men and women aged 70 and older and in good health at the time of enrollment.

MEASUREMENTS

Serum IGF-1, IGFBP-1, and IGFBP-2; fasting serum insulin; fasting serum glucose; visceral fat; and total percent fat.

RESULTS

Higher IGFBP-1 and higher IGFBP-2 were significantly associated with lower fasting insulin, lower fasting glucose, and lower adiposity, but higher IGFBP-1 and IGFBP-2 were associated with greater mortality. In multivariate adjusted models, the hazard ratio for all-cause mortality was 1.48 (95% confidence interval (CI)=1.14-1.92) per standard deviation (SD) increase in IGFBP-2 and 1.34 (95% CI=1.01-1.76) per SD increase in IGFBP-1. No association was found between IGF-1 and all-cause mortality.

CONCLUSIONS

Higher IGFBP-1 and IGFBP-2 are associated with lower adiposity and decreased glucose tolerance but also with greater all-cause mortality. Higher levels of serum IGF-1 binding protein (IGFBP) may indicate greater IGF-1 activity and thus represent an association between higher IGF-1 activity and mortality in humans.

Residents in nursing homes (NHs) experience pain that is underrecognized and undertreated. This pain contributes to a decline in quality of life. Although descriptive studies of pain assessment and management have been conducted, few have been published that critically evaluate interventions to improve pain management. Identification of the strengths and gaps in the current literature is required. A literature search was conducted of clinical trials that evaluated prospective interventions to improve pain management. Information on the intervention type, resident sample and setting, endpoints, and study design were extracted. Studies were classified based on a modification of Donabedian's model of healthcare quality. Four categories of interventions were identified: actor, decision support, treatment, and systems. The search strategy and selection criteria yielded 21 articles. Eleven studies used an actor intervention; of these, eight also employed a systems intervention, and one also used a treatment intervention. Two studies used a decision support intervention, seven used a treatment intervention, and one used a systems intervention. The overall quality of research was uneven in several areas: research design--nine studies were quasi-experimental in nature, endpoints measures were not consistent--three did not perform statistical analysis, and characteristics of the resident samples varied dramatically. In conclusion, the number of high-quality studies of pain management in NHs remains limited. Process endpoints are used as surrogate measures for resident endpoints. Systematic approaches are needed to understand how each type of intervention improves the quality of pain management at the resident level.

We examined the ability of sphingosine-1-phosphate (S1P) to desensitize extracellular signal-related kinase (ERK), a mitogen-activated protein kinase linked to antiapoptotic responses in the heart. In isolated adult mouse cardiomyocytes, S1P (10 nM-5 microM) induced ERK phosphorylation in a time- and dose-dependent manner. S1P stimulation of ERK was completely inhibited by an S1P1/3 subtype receptor antagonist (VPC23019), by a Gi protein inhibitor (pertussis toxin) and by a mitogen-activated protein kinase/ERK kinase inhibitor (PD98059). A selective S1P3 receptor antagonist (CAY10444) had no effect on S1P-induced ERK activation. The selective S1P1 agonist SEW2871 also induced ERK phosphorylation. Activation of ERK by restimulation with 100 nM S1P was suppressed after 1 hour of preincubation with 100 nM S1P but recovered fully the next day, suggesting receptor recycling. Similar results were obtained in protein kinase C epsilon-null cardiomyocytes. Treatment with the nonselective S1P receptor agonist FTY720 for 1 hour also reduced phospho-ERK expression in response to subsequent S1P stimulation. In contrast to S1P, some desensitization to FTY720 persisted after overnight exposure. Cell death induced by hypoxia/reoxygenation was reduced by pretreatment with exogenous S1P. This enhanced survival was abrogated by pretreatment with PD98059, VPC23019, or pertussis toxin. Thus, exogenous S1P induces rapid and reversible S1P1-mediated ERK phosphorylation. S1P-induced adult mouse cardiomyocyte survival requires ERK activation mediated via an S1P1-Gi pathway.

Several previous studies have shown that Attention Deficit Hyperactivity Disorder (ADHD) is common in children with Restless Legs Syndrome and ADHD is more common in adults with this syndrome. This pilot study examined the prevalence of Restless Legs Syndrome in adults with ADHD, showing six of 30 adult ADHD participants (20%) had Restless Legs Syndrome. This estimate exceeds the prevalence (7.2%) for a previously published control group. These six adults had more severe ADHD symptomatology than those without Restless Legs Syndrome based on the overall Conners' Adult ADHD Rating Scale. Such results suggest that symptoms of Restless Legs Syndrome may occur often in adults with ADHD and might worsen the symptoms of ADHD. Replication with a larger sample size is in order.