We aimed to systematically review the efficacy of unfractionated heparin (UFH) or low molecular weight heparins (LMWH) for remission induction in patients with ulcerative colitis (UC).
A literature ...search to April 2011 was performed to identify all randomized trials studying UFH or LMWH use in patients with UC. The Cochrane Risk of Bias Tool was used to assess study quality.
LMWH administered subcutaneously showed no benefit over placebo for any outcome, including clinical remission, and clinical, endoscopic, or histological improvement. High-dose LMWH administered via an extended colon-release tablet demonstrated benefit over placebo for clinical remission (odds ratio OR 2.73; 95% confidence interval CI 1.32-5.67; P = 0.007), clinical improvement (OR 2.99; 95% CI 1.30-6.87; P = 0.01), and endoscopic improvement (OR 2.25; 95% CI 1.01-5.01; P = 0.05) but not endoscopic remission or histologic improvement. LMWH was not beneficial when added to standard therapy for clinical remission, clinical improvement, endoscopic remission, or endoscopic improvement. One study examining UFH versus corticosteroids for the treatment of severe UC demonstrated the inferiority of UFH for clinical improvement. More patients assigned to UFH had rectal hemorrhage as an adverse event.
LMWH administered by extended colon-release tablets may be effective for the treatment of active UC. This benefit needs to be confirmed by further randomized controlled studies. The same benefits were not seen when LMWH was administered subcutaneously at lower doses. There is no evidence to support the use of UFH for the treatment of active UC.
Functional electrical stimulation (FES) can restore control and offset atrophy to muscles after neurological injury. However, FES has not been considered as a method for enhancing CNS regeneration. ...This paper demonstrates that FES dramatically enhanced progenitor cell birth in the spinal cord of rats with a chronic spinal cord injury (SCI). A complete SCI at thoracic level 8/9 was performed on 12 rats. Three weeks later, a FES device to stimulate hindlimb movement was implanted into these rats. Twelve identically-injured rats received inactive FES implants. An additional control group of uninjured rats were also examined. Ten days after FES implantation, dividing cells were marked with bromodeoxyuridine (BrdU). The “cell birth” subgroup (half the animals in each group) was sacrificed immediately after completion of BrdU administration, and the “cell survival” subgroup was sacrificed 7 days later. In the injured “cell birth” subgroup, FES induced an 82–86% increase in cell birth in the lumbar spinal cord. In the injured “cell survival” subgroup, the increased lumbar newborn cell counts persisted. FES doubled the proportion of the newly-born cells which expressed nestin and other markers suggestive of tripotential progenitors. In uninjured rats, FES had no effect on cell birth/survival. This report suggests that controlled electrical activation of the CNS may enhance spontaneous regeneration after neurological injuries.
ABSTRACT
Asthma is a chronic respiratory disease characterized by respiratory symptoms, airway inflammation, airway obstruction and airway hyper‐responsiveness. Asthma is common and directly affects ...10% of Australians, 1–5% of adults in Asia and 300 million people worldwide. It is a heterogeneous disorder with many clinical, molecular, biological and pathophysiological phenotypes. Current management strategies successfully treat the majority of patients with asthma who have access to them. However, there is a subset of an estimated 5–10% of patients with asthma who have severe disease and are disproportionately impacted by symptoms, exacerbations and overall illness burden. The care required for this relatively small proportion of patients is also significant and has a major impact on the healthcare system. A number of new therapies that hold promise for severe asthma are currently in clinical trials or are entering the Australian and international market. However, recognition of severe asthma in clinical practice is variable, and there is little consensus on the best models of care or how to integrate emerging and often costly therapies into current practice. In this article, we report on roundtable discussions held with severe asthma experts from around Australia, and make recommendations about approaches for better patient diagnosis and assessment. We assess current models of care for patient management and discuss how approaches may be optimized to improve patient outcomes. Finally, we propose mechanisms to assess new therapies and how to best integrate these approaches into future treatment.
Research Highlights: Two genets of Armillaria altimontana Brazee, B. Ortiz, Banik, and D.L. Lindner and five genets of Armillaria solidipes Peck (as A. ostoyae Romagnesi Herink) were identified and ...spatially mapped within a 16-year-old western white pine (Pinus monticola Doug.) plantation, which demonstrated distinct spatial distribution and interspecific associations. Background and Objectives: A. solidipes and A. altimontana frequently co-occur within inland western regions of the contiguous USA. While A. solidipes is well-known as a virulent primary pathogen that causes root disease on diverse conifers, little has been documented on the impact of A. altimontana or its interaction with A. solidipes on growth, survival, and the Armillaria root disease of conifers. Materials and Methods: In 1971, a provenance planting of P. monticola spanning 0.8 ha was established at the Priest River Experimental Forest in northern Idaho, USA. In 1987, 2076 living or recently dead trees were measured and surveyed for Armillaria spp. to describe the demography and to assess the potential influences of Armillaria spp. on growth, survival, and the Armillaria root disease among the study trees. Results: Among the study trees, 54.9% were associated with Armillaria spp. The genets of A. altimontana and A. solidipes comprised 82.7% and 17.3% of the sampled isolates (n = 1221) from the study plot, respectively. The mapped distributions showed a wide, often noncontiguous, spatial span of individual Armillaria genets. Furthermore, A. solidipes was found to be uncommon in areas dominated by A. altimontana. The trees colonized by A. solidipes were associated with a lower tree growth/survival and a substantially higher incidence of root disease than trees colonized only by A. altimontana or trees with no colonization by Armillaria spp. Conclusions: The results demonstrate that A. altimontana was not harmful to P. monticola within the northern Idaho planting. In addition, the on-site, species-distribution patterns suggest that A. altimontana acts as a long-term, in situ biological control of A. solidipes. The interactions between these two Armillaria species appear critical to understanding the Armillaria root disease in this region.
The relative depletion of high field strength elements (HFSE), such as Nb, Ta and Ti, on normalised trace-element plots is a geochemical proxy routinely used to fingerprint magmatic processes linked ...to Phanerozoic subduction. This proxy has increasingly been applied to ultramafic-mafic units in Archaean cratons, but as these assemblages have commonly been affected by high-grade metamorphism and hydrothermal alteration/metasomatism, the likelihood of element mobility is high relative to Phanerozoic examples. To assess the validity of HFSE anomalies as a reliable proxy for Archaean subduction, we here investigate their origin in ultramafic rocks from the Ben Strome Complex, which is a 7 km2 ultramafic-mafic complex in the Lewisian Gneiss Complex of NW Scotland. Recently interpreted as a deformed layered intrusion, the Ben Strome Complex has been subject to multiple phases of high-grade metamorphism, including separate granulite- and amphibolite-facies deformation events. Additional to bulk-rock geochemistry, we present detailed petrography, and major- and trace-element mineral chemistry for 35 ultramafic samples, of which 15 display negative HFSE anomalies. Our data indicate that the magnitude of HFSE anomalies in the Ben Strome Complex are correlated with light rare earth-element (LREE) enrichment likely generated during interaction with H2O and CO2-rich hydrothermal fluids associated with amphibolitisation, rather than primary magmatic (subduction-related) processes. Consequently, we consider bulk-rock HFSE anomalies alone to be an unreliable proxy for Archaean subduction in Archaean terranes that have experienced multiple phases of high-grade metamorphism, with a comprehensive assessment of element mobility and petrography a minimum requirement prior to assigning geodynamic interpretations to bulk-rock geochemical data.
Objective Normal tissues, including the central nervous system, tolerate single exposures to narrow planes of synchrotron-generated x-rays (microplanar beams; microbeams) up to several hundred Gy. ...The repairs apparently involve the microvasculature and the glial system. We evaluate a hypothesis on the involvement of bystander effects in these repairs. Methods Confluent cultures of bovine aortic endothelial cells were irradiated with three parallel 27-μm microbeams at 24 Gy. Rats' spinal cords were transaxially irradiated with a single microplanar beam, 270 μm thick, at 750 Gy; the dose distribution in tissue was calculated. Results Within 6 hours following irradiation of the cell culture the hit cells died, apparently by apoptosis, were lost, and the confluency was maintained. The spinal cord study revealed a loss of oligodendrocytes, astrocytes, and myelin in 2 weeks, but by 3 months repopulation and remyelination was nearly complete. Monte Carlo simulations showed that the microbeam dose fell from the peak's 80% to 20% in 9 μm. Conclusions In both studies the repair processes could have involved “beneficial” bystander effects leading to tissue restoration, most likely through the release of growth factors, such as cytokines, and the initiation of cell-signaling cascades. In cell culture these events could have promoted fast disappearance of the hit cells and fast structural response of the surviving neighboring cells, while in the spinal cord study similar events could have been promoting angiogenesis to replace damaged capillary blood vessels, and proliferation, migration, and differentiation of the progenitor glial cells to produce new, mature, and functional glial cells.
Oral corticosteroids (OCS) carry serious health risks. Innovative treatment options are required to reduce excessive exposure and promote OCS stewardship.
This study evaluated the trajectories of OCS ...exposure (prednisolone-equivalent) in patients with severe eosinophilic asthma before and after starting mepolizumab and the predictors of becoming OCS free after 6 months of mepolizumab therapy.
This real-world observational study included 309 patients from the Australian Mepolizumab Registry who were followed up for 1 year (n = 225).
Patients had a median age of 60 (interquartile range: 50, 68) years, and 58% were female. At baseline, 48% used maintenance OCS, 96% had ≥1 OCS burst, and 68% had received ≥1 g of OCS in the previous year. After commencing mepolizumab, only 55% of those initially on maintenance OCS remained on this treatment by 12 months. Maintenance OCS dose reduced from median 10 (5.0, 12.5) mg/day at baseline to 2 (0, 7.0) mg/day at 12 months (P < .001). Likewise, proportions of patients receiving OCS bursts in the previous year reduced from 96% at baseline to 50% at 12 months (P < .001). Overall, 137 (48%) patients required OCS (maintenance/burst) after 6 months' mepolizumab therapy. Becoming OCS free was predicted by a lower body mass index (odds ratio: 0.925; 95% confidence interval: 0.872-0.981), late-onset asthma (1.027; 1.006-1.048), a lower Asthma Control Test score (1.111; 0.011-1.220), and not receiving maintenance OCS therapy at baseline (0.095; 0.040-0.227).
Mepolizumab led to a significant and sustained reduction in OCS dependence in patients with severe eosinophilic asthma. This study supports the OCS-sparing effect of mepolizumab and highlights the pivotal role of mepolizumab in OCS stewardship initiatives.
Abstract Therapeutic trials in Duchenne Muscular Dystrophy (DMD) exclude young boys because traditional outcome measures rely on cooperation. The Bayley III Scales of Infant and Toddler Development ...(Bayley III) have been validated in developing children and those with developmental disorders but have not been studied in DMD. Expanded Hammersmith Functional Motor Scale (HFMSE) and North Star Ambulatory Assessment (NSAA) may also be useful in this young DMD population. Clinical evaluators from the MDA-DMD Clinical Research Network were trained in these assessment tools. Infants and boys with DMD ( n = 24; 1.9 ± 0.7 years) were assessed. The mean Bayley III motor composite score was low (82.8 ± 8; p ⩽ .0001) (normal = 100 ± 15). Mean gross motor and fine motor function scaled scores were low (both p ⩽ .0001). The mean cognitive comprehensive ( p = .0002), receptive language ( p ⩽ .0001), and expressive language ( p = .0001) were also low compared to normal children. Age was negatively associated with Bayley III gross motor ( r = −0.44; p = .02) but not with fine motor, cognitive, or language scores. HFMSE ( n = 23) showed a mean score of 31 ± 13. NSAA ( n = 18 boys; 2.2 ± 0.4 years) showed a mean score of 12 ± 5. Outcome assessments of young boys with DMD are feasible and in this multicenter study were best demonstrated using the Bayley III.
This manuscript is a review of the theoretical and clinical concepts provided during an inter-institutional training program on Activity-Based Restorative Therapies (ABRT) and the perceptions of ...those in attendance. ABRT is a relatively recent high volume and intensity approach toward the restoration of neurological deficits and decreasing the risk of secondary conditions associated with paralysis after spinal cord injury (SCI). ABRT is guided by the principle of neuroplasticity and the belief that even those with chronic SCI can benefit from repeated activation of the spinal cord pathways located both above and below the level of injury. ABRT can be defined as repetitive-task specific training using weight-bearing and external facilitation of neuromuscular activation. The five key components of ABRT are weight-bearing activities, functional electrical stimulation, task-specific practice, massed practice and locomotor training which includes body weight supported treadmill walking and water treadmill training. The various components of ABRT have been shown to improve functional mobility, and reverse negative body composition changes after SCI leading to the reduction of cardiovascular and other metabolic disease risk factors. The consensus of those who received the ABRT training was that ABRT has much potential for enhancement of recovery of those with SCI. Although various institutions have their own strengths and challenges, each institution was able to initiate a modified ABRT program.
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