Effects on Smokers of Exposure to Graphic Warning Images

Background and Objectives : Several countries have introduced graphic warning images aimed at discouraging smoking. The objective of this study was to evaluate the impact on smokers of graphic warnings showing cosmetically important harm caused by smoking. Methods : Fifty‐six adult smokers were randomly assigned to view either written smoking warnings or the same written warnings with related graphic images. The smokers viewed the warnings at a rate of one per week for 4 weeks. The smokers were assessed before and after the warnings with regard to stage of change toward smoking cessation and level of smoking. Results : The randomized control trial showed that the warnings with graphic images led to significantly more progress in stage of change toward smoking cessation than written warnings alone. However, the images did not lead to decreases in smoking rates. Conclusions and Scientific Significance : The results indicate that written smoking warnings accompanied by images of cosmetically important harm caused by smoking have more potential than warnings alone in prompting changes in the direction of quitting. (Am J Addict 2012;21:555–557)     

Prenatal exposure to polychlorinated biphenyls and asthma,eczema/hay fever,and frequent ear infections

Objectives: The effects of prenatal exposure to Polychlorinated biphenyls (PCBs) on the development of asthma, frequent ear infections, and eczema/hay fever are not well understood. We aim to investigate associations between prenatal PCB exposure and these health outcomes in the offspring of women who worked at the LaSalle Electrical Utilities Company (EUC). Methods: A retrospective cohort with at least one live birth and known employment time at EUC was eligible for this analysis. Exposure was defined and categorized by the number of fiscal quarters worked during the PCB era (1952–1981). A total of 288 women with 800 live births were included. A Chi-Square test was used to compare maternal and child characteristics across exposure groups and repeated measures logistic regression, controlling for clustering among siblings, was used to assess the associations between prenatal PCB exposure and these outcomes. Results: After adjustment for confounding and independent maternal predictors, 1–4 quarters of prenatal exposure to PCBs increased the odds for asthma (OR 3.24[1.30–8.09]), eczema/hay fever (OR 3.29[1.54–7.04]), and frequent ear infections (OR 2.24[1.19–4.22]) when compared with persons unexposed/exposed only to naphthalenes. The significance of the associations varied by exposure period and level of exposure, with the strongest associations in those employed exclusively after 1952 when PCBs were introduced. Conclusions: These results support previous findings of associations of prenatal exposure to PCBs with asthma, eczema/hay fever, and frequent ear infections. Additional prospective studies are needed to confirm these findings. Also required are more precise PCB exposures to separate them from other exposures in occupational settings.     

The complexity of HIV vasculopathy

We present a case and discuss stroke related to human immunodeficiency virus (HIV) infection and the difficulties of reaching a firm diagnosis of the cause of the aneurysmal vasculopathy. In the absence of a clear aetiology we suggest looking for varicella zoster virus (VZV) replication in the cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) and treating with intravenous acyclovir, aiming for HIV control with appropriate antiretroviral therapy and providing suitable antiplatelet agents. If there is a high index of suspicion of VZV, therapy with acyclovir may be prudent even if the CSF PCR is negative (as may occur after the first 2 weeks of reactivation of infection). Determination of a VZV plasma:CSF IgG ratio is not readily available and would only provide surrogate support for a previous VZV infection in the central nervous system compartment.     

High abundance of CD271(+) multipotential stromal cells (MSCs) in intramedullary cavities of long bones

Aspiration of iliac crest bone marrow (ICBM) remains the most frequent technique used in harvesting multipotential stromal cells (MSCs) for bone regeneration. Although this tissue type is easily accessed by a surgeon, it has a low frequency of MSCs, which is significant given the high cell numbers required for bone regeneration strategies. Lipoaspirates possess higher MSC frequencies, albeit cells with a differentiation profile less suited to orthopaedic interventions. Intra-medullary cavities of long bones have previously been shown to harbour MSCs in animals, however evaluation of their frequency, differentiation capacity and phenotype in humans had not previously been performed. Long bone fatty bone marrow (LBFBM) was collected prior to harvesting bone graft. Basic cellular compositions of donor-matched LBFBM and ICBM aspirates, including the numbers of CD34(+) hematopoietic stem cells and CD31(+) endothelial cells, were similar. MSCs were enumerated using colony-forming-unit-fibroblast assays and flow cytometry for the presence of a resident LBFBM CD45(-/low) CD271(+) MSC population and revealed a trend for higher MSC numbers (average 5 fold, n=6) per millilitre of LBFBM compared to donor-matched ICBM. Functional characteristics of resident MSCs, including their growth rates, differentiation potentials and surface phenotypes (CD73(+)CD105(+)CD90(+)) before and after culture-amplification, were similar. Enhanced numbers of MSCs could be recovered following brief enzymatic treatment of solid fragments of LBFBM. Our findings therefore reveal that the intramedullary cavity of the human femur is a depot of MSCs, which, although closely associated with fat, have a differentiation profile equivalent to ICBM. This anatomical site is frequently accessed by the orthopaedic/trauma surgeon and aspiration of the intramedullary cavity represents a 'low-tech' method of harvesting potentially large numbers of MSCs for regenerative therapies and research.     

Non-steroidal anti-inflammatory drug use and the risk of benign prostatic hyperplasia-related outcomes and nocturia in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Study Type – Therapy (cohort) Level of Evidence 4 What's known on the subject? and What does the study add? Accumulating evidence suggests that inflammation may contribute to the development of BPH and LUTS. Therefore, it is plausible that anti‐inflammatory agents, such as aspirin and other NSAIDs, may reduce the risk of BPH/LUTS, as was observed in a recent analysis of daily aspirin use and BPH/LUTS risk in the Olmsted County Study of Urinary Symptoms and Health Status in Men. The present study, conducted in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, found no association for recent aspirin or ibuprofen use with the risk of BPH/LUTS.

OBJECTIVE

• ? To investigate the relationship between non‐steroidal anti‐inflammatory drug (NSAID) use and the incidence of benign prostatic hyperplasia (BPH)‐related outcomes and nocturia, a lower urinary tract symptom (LUTS) of BPH, in light of accumulating evidence suggesting a role for inflammation in BPH/LUTS development.

PATIENTS AND METHODS

• ? At baseline, participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial completed questions on recent, regular aspirin and ibuprofen use, BPH surgery, diagnosis of an enlarged prostate/BPH, and nocturia. Participants in the intervention arm also underwent a digital rectal examination (DRE), from which prostate dimensions were estimated, as well as a prostate‐specific antigen (PSA) test. Only participants in the intervention arm without BPH/LUTS at baseline were included in the analysis (n= 4771).
• ? During follow‐up, participants underwent annual DREs and PSA tests, provided annual information on finasteride use, and completed a supplemental questionnaire in 2006–2008 that included additional questions on diagnosis of an enlarged prostate/BPH and nocturia.
• ? Information collected was used to investigate regular aspirin or ibuprofen use in relation to the incidence of six BPH/LUTS definitions: diagnosis of an enlarged prostate/BPH, nocturia (waking two or more times per night to urinate), finasteride use, any self‐reported BPH/LUTS, prostate enlargement (estimated prostate volume ≥30 mL on any follow‐up DRE) and elevation in PSA level (>1.4 ng/mL on any follow‐up PSA test).

RESULTS

• ? Generally, null results were observed for any recent, regular aspirin or ibuprofen use (risk ratio = 0.92–1.21, P= 0.043–0.91) and frequency of use (risk ratios for one category increase in NSAID use = 0.98–1.11, P‐trends = 0.10–0.99) with incident BPH/LUTS.

CONCLUSION

• ? The findings obtained in the present study do not support a protective role for recent NSAID use in BPH/LUTS development.

     

Relationship of physical therapy inpatient rehabilitation interventions and patient characteristics to outcomes following spinal cord injury: The SCIRehab project

Background/objective

Examine associations of type and quantity of physical therapy (PT) interventions delivered during inpatient spinal cord injury (SCI) rehabilitation and patient characteristics with outcomes at the time of discharge and at 1 year post-injury.

Methods

Physical therapists delivering routine care documented details of PT interventions provided. Regression modeling was used to predict outcomes at discharge and 1 year post-injury for a 75% subset; models were validated with the remaining 25%. Injury subgroups also were examined: motor complete low tetraplegia, motor complete paraplegia, and American Spinal Injury Association (ASIA) Impairment Scale (AIS) D motor incomplete tetra-/paraplegia.

Results

PT treatment variables explain more variation in three functionally homogeneous subgroups than in the total sample. Among patients with motor complete low tetraplegia, higher scores for the transfer component of the discharge motor Functional Independence Measure () are strongly associated with more time spent working on manual wheelchair skills. Being male is the most predictive variable for the motor FIM score at discharge for patients with motor complete paraplegia. Admission ASIA lower extremity motor score (LEMS) and change in LEMS were the factors most predictive for having the primary locomotion mode of “walk” or “both (walk and wheelchair)” on the discharge motor FIM for patients with AIS D injuries.

Conclusion

Injury classification influences type and quantity of PT interventions during inpatient SCI rehabilitation and is a strong predictor of outcomes at discharge and 1 year post-injury. The impact of PT treatment increases when patient groupings become more homogeneous and outcomes become specific to the groupings.

Note

This is the second of nine articles in the SCIRehab series.     

Effects of JAK3 inhibition with CP-690,550 on immune cell populations and their functions in nonhuman primate recipients of kidney allografts

BACKGROUND: Janus Kinase (JAK) 3 is a tyrosine kinase essential for proper signal transduction downstream of selected cytokine receptors and for robust T-cell and natural killer cells activation and function. JAK3 inhibition with CP-690,550 prevents acute allograft rejection. To provide further insight into the mechanisms of efficacy, we investigated the immunomodulatory effects of CP-690,550 in vitro and in vivo in nonhuman primates. METHODS: Pharmacodynamic assessments of lymphocyte activation, function, proliferation and phenotype were performed in three settings: in vitro in whole blood isolated from untransplanted cynomolgus monkeys (cynos), in vivo in blood from untransplanted cynos dosed with CP-690,550 for 8 days, and in vivo in blood from transplanted cynos immunosuppressed with CP-690,550. Cell surface activation markers expression, IL-2- enhanced IFN-gamma production, lymphocyte proliferation and immune cell phenotype analyzes were performed with multiparametric flow cytometry. RESULTS: In vitro exposure to CP-690,550 resulted in significant reduction of IL-2-enhanced IFN-gamma production by T-cells (maximum inhibition of 55-63%), T-cell surface expression of CD25 (50% inhibitory concentration (IC50); 0.18 microM) and CD71 (IC50; 1.6 microM), and T-cell proliferative capacities measured by proliferating cell nuclear antigen expression (IC50; 0.87 microM). Similar results were observed in animals dosed with CP-690,550. In addition, transplanted animals displayed significant reduction of NK cell (90% from baseline) and T-cell numbers whereas CD8 effector memory T-cell populations were unaffected. CONCLUSIONS: Potent in vitro and in vivo immunomodulatory effects of the JAK3 inhibitor CP-690,550 likely contribute to its efficacy in the prevention of organ allograft rejection.