Maternal administration of granulocyte colony-stimulating factor improves neonatal rat survival after a lethal group B streptococcal infection

Maternally administered recombinant human granulocyte colony- stimulating factor (rhG-CSF) has been shown to cross the placenta and induce a peripheral neutrophilia and increases in the marrow and spleen neutrophil storage pools in fetal and newborn rats. In the present study, we have used this model system to investigate the efficacy of prenatally administered rhG-CSF on neonatal defense to a lethal challenge with Group B-beta hemolytic Streptococcus (GBS). Pregnant rats were injected with rhG-CSF twice daily beginning 6 days before parturition. At birth, all pups were infected with a dose of GBS that is lethal for 90% of infected pups (LD90). Survival was monitored daily for 5 days. Survival of infected pups from saline-treated mothers beyond 60 hours after infection was 10%. No difference in survival was observed among pups from mothers treated 2 and 4 days before parturition. In contrast, we determined that survival was 82.5% among infected pups from mothers treated for 6 days before parturition with rhG-CSF. Our results demonstrate that maternal administration of rhG- CSF augments neonatal defenses against a lethal bacterial challenge.     

Granulocyte-macrophage colony-stimulating factor augmentation of T-cell receptor-dependent and T-cell receptor-independent thymocyte proliferation

The effects of granulocyte-macrophage colony-stimulating factor (GM- CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T- cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)-mediated proliferation of unseparated thymocyte populations. To identify the GM- CSF responsive cell type, thymic AC and T cells were examined for GM- CSF responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte proliferation appears to be mediated via augmentation of AC function, and not via direct effects on mature single-positive (SP) thymocytes. Enriched double-negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF induced the proliferation of adult and fetal DN thymocytes in an AC-independent and TCR-independent single- cell assay. Thus, in contrast to the SP thymocytes, a DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may play a direct role in the expansion of DN thymocytes and an indirect role in the expansion of SP thymocytes.     

Medication administration errors and mortality: Incidents reported in England and Wales between 2007 ̶ 2016

BackgroundMedication administration errors may contribute to patient mortality, thus additional understanding of such incidents is required.ObjectivesTo analyse medication administration errors reported in acute care resulting in death, to identify the drugs concerned, and to describe medication administration error characteristics (location of error, error type, patient's age) by drug group.MethodsMedication administration errors reported in acute care in 2007 ? 2016 (n = 517,384) were obtained from the National Reporting and Learning System for England and Wales. Incidents reported as resulting in death (n = 229) were analysed. Drugs were classified by two researchers using the British National Formulary. Drug categories were described by medication administration errors' year, location, patient age, and error category based on the incidents’ original classification.ResultsErrors were most often reported on wards (66.4%, n = 152), and in patients aged over 75 years (41.5%, n = 95). The most common error category was omitted medicine or ingredient (31.4%, n = 72); most common drug groups were cardiovascular (20.1%, n = 46) and nervous system (10.0%, n = 23). Most errors in patients under 12 years concerned drugs to treat infection; cardiovascular drugs were most common among other age groups.ConclusionsIn order to prevent these most serious of medication administration errors, interventions should focus on avoiding dose omissions, and administration of drugs for patients over 75 years old, as well as safe administration of parenteral anticoagulants and antibacterial drugs.     

Nonvolitional assessment of muscle endurance in idiopathic inflammatory myopathies: There is no relationship between patient‐reported fatigue and muscle fatigability

Introduction: We investigated whether muscle endurance differs between IIM patients and controls and if a relationship exists between perceived fatigue and poor muscle endurance. Methods: Quadriceps contractility, measured using femoral nerve stimulation (TwQ), and strength, measured using maximal voluntary contraction (MVCQ), were assessed in 20 IIM patients and matched controls. Quadriceps endurance was assessed using repetitive electrical stimulation (3 minutes). Time for force to fall to 70% initial force was determined (T70). Reported fatigue was measured using the FACIT‐F/Fatigue Severity Scales. Results: TwQ and MVCQ were lower and perceived fatigue greater for patients. There was no difference in T70 between groups. No relationships were observed between perceived fatigue and endurance (T70). Conclusions: IIM patients reported more fatigue and were weaker than controls, but there was no difference in muscle endurance. Endurance and strength were unrelated to reported fatigue measures. Mechanisms driving perceived IIM fatigue are likely to be multifactorial. Muscle Nerve 50 : 401–406, 2014     

Quantitative tissue pH measurement during cerebral ischemia using amine and amide concentration-independent detection (AACID) with MRI

Tissue pH is an indicator of altered cellular metabolism in diseases including stroke and cancer. Ischemic tissue often becomes acidic due to increased anaerobic respiration leading to irreversible cellular damage. Chemical exchange saturation transfer (CEST) effects can be used to generate pH-weighted magnetic resonance imaging (MRI) contrast, which has been used to delineate the ischemic penumbra after ischemic stroke. In the current study, a novel MRI ratiometric technique is presented to measure absolute pH using the ratio of CEST-mediated contrast from amine and amide protons: amine/amide concentration-independent detection (AACID). Effects of CEST were observed at 2.75 parts per million (p.p.m.) for amine protons and at 3.50 p.p.m. for amide protons downfield (i.e., higher frequency) from bulk water. Using numerical simulations and in vitro MRI experiments, we showed that pH measured using AACID was independent of tissue relaxation time constants, macromolecular magnetization transfer effects, protein concentration, and temperature within the physiologic range. After in vivo pH calibration using phosphorus (³¹P) magnetic resonance spectroscopy (³¹P-MRS), local acidosis is detected in mouse brain after focal permanent middle cerebral artery occlusion. In summary, our results suggest that AACID represents a noninvasive method to directly measure the spatial distribution of absolute pH in vivo using CEST MRI.