Reticulocytes bearing C4d as biomarkers of disease activity for systemic lupus erythematosus

OBJECTIVE: There is an urgent need for biomarkers with which to monitor disease activity in patients with systemic lupus erythematosus (SLE). We recently showed that abnormal levels of C4d, an activation-derived fragment of complement component C4, are deposited on the surface of erythrocytes from patients with SLE. This study focused on reticulocytes, the youngest and shortest-lived erythrocytes (lifespan 24-48 hours), with the objective of testing our hypothesis that when reticulocytes emerge from the bone marrow, they are immediately exposed to and acquire C4d at levels proportionate to the extent of complement activation at that time, thereby reflecting disease activity in SLE. METHODS: We conducted a cross-sectional study of 156 patients with SLE, 140 patients with other diseases, and 159 healthy controls. Levels of C4d on the surface of reticulocytes were examined using a 2-color flow cytometric assay. The results were analyzed for correlations with SLE disease activity. RESULTS: A wide range of increased levels of reticulocyte C4d was specifically detected in SLE patients. These levels fluctuated in SLE patients and correlated with clinical disease activity, as determined by the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus Activity Measure (SLAM). Specifically, in cross-sectional analyses, patients with reticulocyte C4d levels in the highest quartile compared with those in the lowest quartile had significantly higher SELENA-SLEDAI (P = 0.00002) and SLAM (P = 0.02) scores. Longitudinal observation demonstrated that the reticulocyte C4d levels changed in relation to the clinical course in individual patients. CONCLUSION: These findings support our hypothesis that C4d-bearing reticulocytes may serve as biomarkers of disease activity in patients with SLE.     

Maternal Physical Activity Is Associated With Improved Blood Pressure Regulation During Late Pregnancy

Background

Cardiovagal baroreflex gain (cBRG) reflects an individual's ability to buffer swings in blood pressure. It is not well understood how this mechanism is influenced by physical activity in pregnancy. Because pregnant women tend to engage in low levels of moderate-to-vigorous physical activity (MVPA) and high levels of sedentary behaviour, we sought to determine the influence of MVPA and sedentary behaviour on cBRG and mean arterial pressure (MAP) in pregnancy.

In vitro exposure of DE‐71, a penta‐PBDE mixture,on immune endpoints in bottlenose dolphins (Tursiops truncatus) and B6C3F1 mice

Polybrominated diphenyl ethers (PBDEs) are an emerging contaminant of concern with low level exposures demonstrating toxicity in laboratory animals and wildlife, although immunotoxicity studies have been limited. Bottlenose dolphin peripheral blood leukocytes (PBLs) and mouse splenocytes were exposed to environmentally relevant DE‐71 (a penta‐PBDE mixture) concentrations (0–50 µg ml^?1) in vitro. Natural killer (NK) cell activity and lymphocyte (B and T cell) proliferation were evaluated using the parallelogram approach for risk assessment. This study aimed to substantiate results from field studies with dolphins, assess the sensitivities between the mouse model and dolphins, and to evaluate risk using the parallelogram approach. In mouse cells, NK cell activity increased at in vitro doses 0.05, 0.5 and 25 µg DE‐71 ml^?1, whereas proliferation was not modulated. In dolphin cells, NK cell activity and lymphocyte proliferation was not altered after in vitro exposure. In vitro exposure of dolphin PBLs to DE‐71 showed similar results to correlative field studies; NK cell activity in mice was more sensitive to in vitro exposure than dolphins, and the parallelogram approach showed correlation with all three endpoints to predict risk in bottlenose dolphins. Copyright © 2014 John Wiley & Sons, Ltd.     

Use of Imugard IG500 Filters for Preparation of Leukocyte-Poor Blood for Cancer Patients

In order to determine the efficiency of Imugard IG500 filters in producing leukocyte-poor blood (LPB), 109 units of red cell concentrates were processed using cold (4 degrees C) or room temperature saline solution without the application of pressure to the blood bag. The results obtained in terms of red blood cell recovery, white blood cell removal, residual white blood cells, and free hemoglobin in the supernatant of the filtered units are comparable to those processed with the IBM 2991. LPB processed without pressure application to the blood bag and room temperature saline solution can be rapidly, efficiently and safely prepared in any size blood bank/transfusion service. This technique is definitely cost-saving in terms of equipment, software, space and personnel training.     

Meta-analysis of telomere length in 19?713 subjects reveals high heritability,stronger maternal inheritance and a paternal age effect

Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64–0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother–offspring (r=0.42; P-value=3.60 × 10⁻⁶¹) than father–offspring correlation (r=0.33; P-value=7.01 × 10⁻⁵), and a significant positive association with paternal age at offspring birth (β=0.005; P-value=7.01 × 10⁻⁵). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 × 10⁻³⁰) was seen, which appeared stronger in older spouse pairs (mean age ≥55 years; r=0.31; P-value=4.27 × 10⁻²³) than in younger pairs (mean age<55 years; r=0.20; P-value=3.24 × 10⁻¹⁰). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age.     

High resolution muscle measurements provide insights into equinus contractures in patients with cerebral palsy

Muscle contractures that occur after upper motor neuron lesion are often surgically released or lengthened. However, surgical manipulation of muscle length changes a muscle's sarcomere length (L_s), which can affect force production. To predict effects of surgery, both macro‐ (fascicle length (L_f)) and micro‐ (L_s) level structural measurements are needed. Therefore, the purpose of this study was to quantify both L_s and L_f in patients with cerebral palsy (CP) as well as typically developing (TD) children. Soleus ultrasound images were obtained from children with CP and TD children. L_f was determined and, with the joint in the same position, CP biopsies were obtained and formalin fixed, and L_s was measured by laser diffraction. Since soleus L_s values were not measurable in TD children, TD L_s values were obtained using three independent methods. While average L_f did not differ between groups (CP = 3.6 ± 1.2 cm, TD = 3.5 ± 0.9 cm; p > 0.6), L_s was dramatically longer in children with CP (4.07 ± 0.45 µm vs. TD = 2.17 ± 0.24 µm; p < 0.0001). While L_f values were similar between children with CP and TD children, this was due to highly stretched sarcomeres within the soleus muscle. Surgical manipulation of muscle‐tendon unit length will thus alter muscle sarcomere length and change force generating capacity of the muscle. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:33–39, 2015.     

Nerve Transfers for Treatment of Isolated Axillary Nerve Injuries

BACKGROUND:

The most common neurological defect in traumatic anterior glenohumeral dislocation is isolated axillary nerve palsy. Most recover spontaneously; however, some have persistent axillary neuropathy. An intact rotator cuff may compensate for an isolated axillary nerve injury; however, given the high rate of rotator cuff pathology with advancing age, patients with an axillary nerve injury are at risk for complete shoulder disability.

OBJECTIVE:

To review reconstruction of the axillary nerve to alleviate shoulder pain, augment shoulder stability, abduction and external rotation to alleviate sole reliance on the rotator cuff to move and stabilize the shoulder.

METHODS:

A retrospective review of 10 patients with an isolated axillary nerve injury and an intact rotator cuff who underwent a triceps nerve branch to axillary nerve transfer was performed. Patient demographics, surgical technique, deltoid strength, donor-site morbidity, complications and time to surgery were evaluated.

RESULTS:

Ten male patients, mean age 38.3 years (range 18 to 66 years), underwent a triceps to axillary nerve transfer for isolated axillary nerve injury 7.4 months (range five to 12 months) post-traumatic shoulder dislocation. Deltoid function was British Medical Research Council grade 0/5 in all patients preoperatively and ≥3/5 deltoid strength in eight patients at final follow-up (14.8 months [range 12 to 25 months]). There were no complications and no donor-site morbidity.

CONCLUSION:

A triceps to axillary nerve transfer for isolated axillary neuropathy following traumatic shoulder dislocation improved shoulder pain, stability and deltoid strength, and potentially preserves shoulder function with advancing age by alleviating sole reliance on the rotator cuff for shoulder abduction and external rotation.     

Characterization of actions taken during the delivery of medication therapy management: A time-and-motion approach

Objectives

To characterize actions performed by pharmacists and support staff during provision of medication therapy management (MTM) and to compare actions performed according to practice characteristics.

In vitro PFOS exposure on immune endpoints in bottlenose dolphins (Tursiops truncatus) and mice

Previous studies in our lab have shown that perfluorooctane sulfonate (PFOS) modulates immune function in mice and correlates with many immune parameters in bottlenose dolphins (Tursiops truncatus). In this study, bottlenose dolphin peripheral blood leukocytes (PBLs) and adult female B6C3F1 mouse splenocytes were exposed to environmentally relevant PFOS concentrations (0–5 µg ml^–1) in vitro; and natural killer (NK) cell activity and lymphocyte proliferation (T and B cell) were assessed using the parallelogram approach for risk assessment. The objectives were: to corroborate results from the correlative studies in bottlenose dolphins with in vitro PFOS exposures; to evaluate the sensitivity of the mouse model as compared with bottlenose dolphins; and to assess risk using the parallelogram approach. In mouse cells, NK cell activity was decreased at in vitro doses of 0.01, 0.5, 0.1, 0.5 and 1 µg PFOS ml^–1 and increased at 5 µg ml^–1. Additionally, B cell proliferation was not altered, but T cell proliferation was decreased at all in vitro PFOS exposures. In dolphin cells, NK cell activity and T cell proliferation were not altered by in vitro PFOS exposure, but B cell proliferation exhibited a positive association in relation to PFOS dose. Overall, the data indicates that: the in vitro exposures of bottlenose dolphin PBLs exhibited results similar to reported correlative fields studies; that mice were generally more sensitive (for these selected endpoints) than were dolphins; and that the parallelogram approach could be used two‐thirds of the time to predict the effects in bottlenose dolphins. Copyright © 2013 John Wiley & Sons, Ltd.