Release of Proinflammatory Cytokines During Pediatric Cardiopulmonary Bypass: Heparin-Bonded Versus Nonbonded Oxygenators

Background. Heparin bonding of the cardiopulmonary bypass (CPB) circuit may be associated with a reduced inflammatory response and improved clinical outcome. The relative contribution of a heparin-bonded oxygenator (ie, >80% of circuit surface area) to these effects was assessed in a group of pediatric patients.

Methods. Twenty-one pediatric patients undergoing CPB operations were assigned randomly to receive either a heparin-bonded oxygenator (group H, n = 11) or a nonbonded oxygenator (group C, n = 10) in otherwise nonbonded circuits. The two groups were similar in pathology, age, weight, CPB time, and cross-clamp time. Plasma levels of the cytokines tumor necrosis factor-, interleukin-6, and interleukin-8, as well as terminal complement complex, neutrophils, and elastase, were analyzed before, during, and after CPB.

Results. Significant levels of tumor necrosis factor- were not detected in either group. Plasma levels of all other markers increased during and after CPB compared with baseline. Plasma levels of interleukin-6 peaked in both groups 2 hours after the administration of protamine but remained significantly higher in group C 24 hours after operation. Plasma concentrations of interleukin-8 peaked at similar levels in both groups 30 minutes after protamine administration and returned to baseline thereafter. Levels of terminal complement complex and elastase peaked in both groups 30 minutes after protamine administration. Plasma levels of terminal complement complex were significantly higher at the end of CPB and after protamine administration in group C. Elastase levels were significantly higher 2 and 24 hours after CPB in group C. The ventilation time of patients in group H was significantly lower than that of patients in group C: 10 (range, 3 to 24) versus 22 (range, 7 to 24) hours, respectively (p < 0.01).

Conclusions. The present study confirms the proinflammatory nature of pediatric operations and demonstrates a lessened systemic inflammatory response with the use of heparin-bonded oxygenators. This is achieved without bonding of the entire circuit, which could have significant cost-benefit implications by negating the need for custom-built heparin-bonded circuitry.     

Neuroactive pregnanolone isomers during pregnancy

The pregnanolone isomers (PI) allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one), isopregnanolone (3beta-hydroxy-5alpha-pregnan-20-one), epipregnanolone (3beta-hydroxy-5beta-pregnan-20-one), progesterone, and estradiol were measured in 138 pregnant women. The sampling was carried out from the first through the 10th month of pregnancy. Gas chromatography-mass spectrometry analysis and RIA were used for the measurement of steroid levels. The ratios of individual PI were similar to those found previously around parturition: about 25:10:7:1 for allopregnanolone, pregnanolone, isopregnanolone, and epipregnanolone, respectively. All the PI showed a significant increase during pregnancy, which was more pronounced in the 3alpha-steroids. The results indicated changing ratios between 3alpha- and 3beta-PI and between 5alpha- and 5beta-PI throughout pregnancy. The constant allopregnanolone/isopregnanolone ratio found through pregnancy weakened the hypothesis of the role of isopregnanolone in the onset of parturition. The ratio of estradiol (stimulating uterine activity) to 5alpha-PI and epipregnanolone exhibited significant changes during pregnancy in favor of estradiol up to the sixth or seventh month, in contrast to the constant estradiol/pregnanolone ratio. A pregnancy-stabilizing role of pregnanolone, counterbalancing the stimulating effect of estradiol on the onset of parturition, was suggested.     

Novel Mutations in the DYNC1H1 Tail Domain Refine the Genetic and Clinical Spectrum of Dyneinopathies

The heavy chain 1 of cytoplasmic dynein (DYNC1H1) is responsible for movement of the motor complex along microtubules and recruitment of dynein components. Mutations in DYNC1H1 are associated with spinal muscular atrophy (SMA), hereditary motor and sensory neuropathy (HMSN), cortical malformations, or a combination of these. Combining linkage analysis and whole‐exome sequencing, we identified a novel dominant defect in the DYNC1H1 tail domain (c.1792C>T, p.Arg598Cys) causing axonal HMSN. Mutation analysis of the tail region in 355 patients identified a de novo mutation (c.791G>T, p.Arg264Leu) in an isolated SMA patient. Her phenotype was more severe than previously described, characterized by multiple congenital contractures and delayed motor milestones, without brain malformations. The mutations in DYNC1H1 increase the interaction with its adaptor BICD2. This relates to previous studies on BICD2 mutations causing a highly similar phenotype. Our findings broaden the genetic heterogeneity and refine the clinical spectrum of DYNC1H1, and have implications for molecular diagnostics of motor neuron diseases.     

Persistence of Efficacy of 0.1% Cyclosporin A Cationic Emulsion in Subjects with Severe Keratitis Due to Dry Eye Disease: A Nonrandomized,Open-label Extension of the SANSIKA Study

Purpose

Results from a 6-month double-masked and a 6-month open-label study (SANSIKA) established the efficacy and safety of once-daily 0.1% cyclosporin A cationic emulsion (CsA CE) in severe keratitis due to dry eye disease (DED). This article presents results from the Post-SANSIKA study, a 24-month extension of SANSIKA assessing the sustained efficacy of CsA CE after treatment discontinuation.

Power wheelchair driving challenges in the community: a users’ perspective

Purpose: There is limited information on the difficulties individuals experience in manoeuvring their power wheelchairs during daily activities. The aim of this study was to describe the nature and context of power wheelchair driving challenges from the perspective of the user. Methods: A qualitative design using semi-structured interviews with power wheelchair users. Qualitative content analysis was used to identify themes. Results: Twelve experienced power wheelchair users were interviewed. Findings revealed that power wheelchair driving difficulties were related to the accomplishment of activities of daily living, and the influence of environmental context. Four key themes emerged: (1) difficulties accessing and using public buildings-facilities, (2) outdoor mobility, (3) problems in performing specific wheelchair mobility tasks/manoeuvres and (4) barriers and circumstances that are temporary, unforeseen or specific to a particular context. Conclusion: This qualitative study furthers our understanding of the driving difficulties powered wheelchair (PW) users experience during daily activities. This knowledge will assist clinicians and researchers in two areas: in choosing assessment measures that are ecologically valid for power wheelchair users; and, in identifying and refining the content of training programs specific to the use of power wheelchairs.

• Implications for Rehabilitation

• A better understanding of the everyday challenges individuals experience in driving their power wheelchair will assist clinicians and researchers in:

• Choosing assessment measures and identifying training programs for this population.

• Refining the content of power wheelchair training programs.

     

Lifestyle Risk Factors Associated with Arm Swelling Among Women with Breast Cancer

Background

Breast cancer-related lymphedema (BCRL) is a feared complication for breast cancer patients who have undergone axillary surgery. Although clinical risk factors for BCRL are defined, data are sparse regarding common exposures that might induce incident arm swelling. The goal of this study was to quantify the association between common exposures thought to be potential risk factors and the occurrence of incident arm swelling among breast cancer survivors with or at risk for BCRL.

Methods

This is a prospective subanalysis of the Physical Activity and Lymphedema (PAL) trial, a randomized controlled trial of 295 breast cancer survivors. Participants reported their exposure to 30 different potential risk factors at 3 month intervals for 1 year. Incident arm swelling was defined as a ≥5 % increase in interlimb water volume difference between two consecutive time points.

Results

Twenty-seven participants (9 %) experienced incident arm swelling and 268 patients (91 %) did not. Sauna use was the only exposure that was significantly predictive of incident arm swelling (p = 0.05). Nonwhite and nonblack participants had a significantly increased risk for experiencing incident arm swelling (p = 0.005 for both comparisons).

Conclusions

In our patient cohort, many common exposures that have been reported to be risk factors did not prove to have a significant predictive relationship for incident arm swelling. This study supports the recommendation that breast cancer patients who have had axillary surgery should avoid sauna use. The results do not confirm the need for other restrictions that may interfere with the quality of life in women with breast cancer.