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Neuromyelitis optica (NMO), which is also referred to as Devic's disease, was originally considered an aggressive subtype of multiple sclerosis (MS) presenting as optic neuritis and/or extensive transverse myelitis in which 50% of patients become blind or in a wheelchair within 5 years of onset. Subsequently, NMO was categorized as one of a spectrum of inflammatory and demyelinating autoimmune disorders that are distinct from multiple sclerosis and termed neuromyelitis optica spectrum disorder (NMOSD). NMOSD differs from multiple sclerosis by its clinical course, presentation, magnetic resonance imaging findings, clinical presentation, serum biomarker prognosis, and response to treatment. More recently, NMOSD has been subdivided according to auto-antibody status as aquaporin 4 (AQP4) seropositive NMO, myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), and seronegative NMOSD. The only treatment to date that has resulted in treatment-free remissions, now lasting for more than 5-10 years with posttreatment disappearance of anti-AQP4 antibodies, is hematopoietic stem cell transplantation (HSCT) using either an allogeneic (matched sibling or unrelated) donor with a reduced toxicity conditioning regimen or an autologous stem cell source using a nonmyeloablative conditioning regimen of plasmapheresis (PLEX), cyclophosphamide (Cytoxan®), rabbit antithymocyte (ATG), and rituximab (Rituxan®). Post-HSCT long-term resolution of disease activity and disappearance of AQP4 antibodies is consistent with HSCT-induced immune tolerance., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Autologous hematopoietic stem cell transplantation (aHSCT) may be effective in carefully selected pediatric patients with multiple sclerosis (MS), neuromyelitis optica (NMO), and chronic inflammatory demyelinating polyneuropathy (CIDP). aHSCT for pediatric MS (same as for adults) is performed to eradicate inflammatory autoreactive cells with lympho-ablative regimens and restore immune tolerance. Its therapeutic effect in MS relies on various mechanisms: (1) the immunosuppressive conditioning regimen prior to aHSCT was able to eradicate the autoreactive cells and (2) the regeneration/renewal of the immune system to reset the aberrant immune response against self-antigens. The aHSCT procedure includes the following different steps, as described in this chapter: patient selection through careful pretransplant screening, "wash-out" period from previous treatments, mobilization of hematopoietic stem cells (HSC), conditioning regimen, HSC infusion, and posttransplant monitoring for early and late complications. Moreover, specific aspects of pediatric population undergoing aHSCT are described. According to the available evidence, aHSCT appears to be safe in pediatric MS, obtaining disease control for a prolonged time after the procedure. A reasonable approach in this setting includes the application of less toxic treatments while reserving aHSCT procedure for patients with severe/refractory forms of the disease. The EBMT considers MS, NMO, and CIDP in pediatric patients within the category of the clinical option (CO), where candidates for aHSCT can be selected on the basis of careful consideration of individual case history in the multidisciplinary setting., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Autologous hematopoietic stem cell transplantation (HSCT) is associated with 5-year treatment-free remissions in approximately 80% of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who failed or were dependent on intravenous immunoglobulin and or plasmapheresis. Autologous HSCT was associated with significant improvement in strength, independent ambulation, quality of life, nerve conduction velocity, and compound muscle action potential amplitude. The results of HSCT are dependent on proper patient selection, i.e., the right diagnosis and the right stage of the disease. An important caveat is that a significant number of patients with a CIDP diagnostic label are found upon further workup have a peripheral neuropathy of another etiology. Patients undergoing HSCT for CIDP should be reevaluated before HSCT to confirm the diagnosis and those who fail HSCT should be reevaluated for a diagnosis other than CIDP., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Untargeted lipidomics using liquid chromatography high-resolution mass spectrometry (LC-HRMS) was performed using polarity switching, and in positive and negative polarity separately on the same set of serum samples, and the performances of the methods were evaluated. Polarity switching causes an increase in the cycle time of the HRMS measurements (1.18 s/cycle vs 0.27 s/cycle), resulting in fewer data points across chromatographic peaks. The coefficient of variation (CV) was on average lower for the added isotopically labelled standards in pooled samples (QC) and patient samples using separate polarities (QC = 5.6%, samples = 12.5%) compared to polarity switching (QC = 8.5%, samples = 13.4%), but the difference was not statistically significant. For the endogenous features measured in the QCs polarity switching resulted in on average significantly higher CVs (3.80 (p = 4.25e-30) and 3.3 percentage points (p = 6.84e-40), for positive and negative modes, respectively) however still acceptable for an untargeted method (mean CVs of 17.9% and 12.2% in positive and negative modes respectively). A slightly larger number of endogenous features were detected using the separate polarities, but the large majority of features (>95%) were detected with both methodologies. The overlap of features detected in both positive and negative polarities was low (4.1%) demonstrating the importance of using both polarities for untargeted lipidomics. When investigating the effects of a treatment on multiple sclerosis patients it was found that both methodologies gave highly similar biological results, further confirming the applicability of polarity switching., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The prevalence of epilepsy is increased in multiple sclerosis (MS), but information on AED treatment and seizure outcome is scarce. We describe epilepsy characteristics including the use of AEDs and proportion of seizure-free patients at two tertiary hospitals in Sweden., Method: We retrospectively studied electronic medical records of all patients with a diagnosis of MS and seizures at Sahlgrenska university hospital and Uppsala university hospital. Clinical data were reviewed until 2017., Results: We identified a total of 62 MS patients with at least one seizure. Median age at the first seizure (before or after MS) was 41 years (range 0-80). The most common MS disease course at the first seizure was secondary progressive MS, the neurological disability was considerable, and most patients had several MRI lesions at their first seizure. The first EEG demonstrated epileptiform discharges in 38% and unspecific pathology in 40%. Current seizure status could be determined for 37 patients. Out of these, 46% had been seizure free for more than one year at last follow-up. The majority of patients (65%) were on monotherapy at last follow-up. Carbamazepine was the most commonly used first AED, with a retention rate of 52%. No individual AED was associated with a particularly high rate of seizure freedom. The most common reason for discontinuation of the first AED was side-effects., Conclusion: Seizure freedom rates were low, perhaps indicating a need for higher ambitions in management. Side effects of AEDs may be a particular concern when treating epilepsy in patients with MS., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Live fire military training involves the detonation of explosive warheads on training ranges. The purpose of this experiment is to evaluate the hydrogeological changes to the vadose zone caused by military training with high explosive ammunition. In particular, this study investigates artillery ammunition which penetrates underground prior to exploding, either by design or by defective fuze mechanisms. A 105 mm artillery round was detonated 2.6 m underground, and hydraulic conductivity measurements were taken before and after the explosion. A total of 114 hydraulic conductivity measurements were obtained within a radius of 3m from the detonation point, at four different depths and at three different time periods separated by 18months. This data was used to produce a three dimensional numerical model of the soil affected by the exploding artillery round. This model was then used to investigate potential changes to aquifer recharge and contaminant transport caused by the detonating round. The results indicate that an exploding artillery round can strongly affect the hydraulic conductivity in the vadose zone, increasing it locally by over an order of magnitude. These variations, however, appear to cause relatively small changes to both local groundwater recharge and contaminant transport., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Coronary ischaemic syndromes are associated with neutrophil activation. The Bayer automated haematology analysers can detect increased light scatter of neutrophil populations, which correlates with neutrophil activation. We aimed to assess the role of an automated analyser in detecting systemic neutrophil activation in peripheral blood samples of patients with coronary ischaemia., Methods: A prospective cross-sectional study was undertaken in 18 patients with chronic stable angina, 9 with unstable angina and 26 normal control subjects. Whole blood samples were taken to assess neutrophil count and light scatter, and serum samples were taken from some patients for assessment of Troponin T, C-reactive protein (CRP) and myeloperoxidase (MPO). In addition, whole blood was stimulated in vitro with interleukin (IL)-8 and N-formyl-methionyl-leucyl-phenylalanine (fMLP) to assess changes in neutrophil light scatter detected by the analyser., Results: Neutrophil light scatter was increased in patients with chronic stable and unstable angina compared to normal control subjects (normal subjects 74.1 (73.3, 75.0) (mean arbitrary units (95% confidence intervals, (CI)) vs. 78.6 (76.9, 80.3) in the chronic stable angina group P<0.001 and 77.1 (75.3, 79.0) in the unstable angina group P<0.007). In vitro stimulation of whole blood produced comparable increases in neutrophil light scatter when morphological changes in neutrophils were demonstrable under electron microscopy., Conclusions: Automated measurement of neutrophil activation by light scatter is possible using the Advia 120 analyser and is superior to a neutrophil count in discriminating groups with angina. This technique may be useful in monitoring disease activity and progression in coronary artery disease and in guiding the use of anti-inflammatory therapies.

A prospective randomized double-blind study was performed to determine the effects of three colloids, Haemaccel, Gelofusine and albumin, and also saline on platelet activation, platelet aggregation (induced by adenosine diphosphate (ADP), epinephrine, collagen) platelet agglutination by ristocetin and other hemostatic variables in 55 patients undergoing primary unilateral total hip replacement. The fluids were administered according to normal clinical practice and assessments were made immediately before, at the end, and 2 h after the end of surgery. Surgery was accompanied by thrombin generation (increases in thrombin/antithrombin III complex, prothrombin F1 +2 fragment) platelet activation (betaTG) and compromised coagulation. Generally, the platelet activation appeared to result in platelet desensitization and brought about a persistent reduction in platelet aggregation to ADP and epinephrine, irrespective of the fluid used. Additionally, Haemaccel and Gelofusine inhibited ristocetin-induced platelet agglutination and albumin inhibited collagen-induced platelet aggregation. Gross inhibitory effects of Haemaccel that had been predicted from an earlier in vitro study did not occur. Particular fluids had selective additional effects on the hemostatic system. Albumin infusion served to maintain plasma albumin at normal concentrations postsurgery. The two gelatin preparations, Haemaccel and Gelofusine, maintained plasma viscosity. All three colloids led to a transient increase in activated partial thromboplastin time postsurgery and also a transient fall in the concentration of factor VIII, which were accompanied by a transient increase in bleeding time, but there was no measurable increase in blood loss. Inhibition of platelet aggregation by certain colloids may provide additional protection against the increased thrombotic risk in patients following major surgery.

During cardiopulmonary bypass, thrombin is generated, which is thought to be initiated by activation of factor XII on the surface of the bypass equipment. We present a patient with severe factor XII deficiency who underwent cardiac surgery. As much thrombin was formed during cardiopulmonary bypass (measured by the prothrombin activation fragment F1 + 2 and thrombin-antithrombin complexes) as in normal patients, showing that factor XII was not necessary for thrombin generation. Factor X, but not factor IX, was activated (as measured by their activation peptides), and this activation correlated with F1 + 2 and thrombin-antithrombin complexes, suggesting that the tissue-factor/factor-VIIa pathway is the trigger for thrombin formation.

Between September 1, 1989, and August 31, 1990, 516 patients were admitted to the Royal Brompton National Heart and Lung Hospital for thoracic operations. A prospective audit recorded the nature and extent of operation, the histologic diagnosis, and the number of units of blood prepared and transfused during hospitalization. Cross-matched blood was requested in 243 patients but only 16.1% of these received transfusion. In total, 1,295 units of whole blood or red cell concentrate were cross-matched and made immediately available in the operating suite at the time of operation. Only 322 units were administered (cross-match to transfusion ratio of 4.02:1). Almost half of the patients who received transfusions received 2 units or less, a third received 3 or 4 units, 10% between 5 and 10 units, and 8.4% required more than 10 units during their hospital stay. The nature and extent of resection was an indicator of the need for transfusion. Other important predisposing factors included a previous thoracic operation, resection for inflammatory disease, decortication of empyema thoracis, chest wall resection, or thoracoplasty. Other thoracic procedures such as pleurodesis, pleurectomy, open lung biopsy, pectus correction, operation for bullous lung disease, and mediastinoscopy had a negligible transfusion requirement. The data suggest that understanding risk factors for transfusion requirements of patients undergoing thoracic surgical procedures should optimize present resources. This is critical when exploiting the limited availability of donated blood and blood products. Similarly, anticipation of transfusion requirements takes best advantage of manpower within the blood bank and minimizes unnecessary and avoidable blood wastage and expenditure.

In a prospective study the incidence of megaloblastic change after ventilation with nitrous oxide for periods of up to 24 h has been determined and the cause of the altered D.N.A. synthesis studied with the deoxyuridine (dU) suppression test in 22 patients undergoing cardiac bypass surgery. 8 patients who received nitrous oxide and oxygen for 24 h had megaloblastic bone-marrow aspirates and abnormal dU suppression tests at the end of ventilation. 5 patients who received no nitrous oxide had normoblastic aspirates and normal dU suppression test. Of the remaining 9 patients, who received nitrous oxide during the operation only, 3 had abnormal dU suppression tests at 24 h. The abnormality revealed by the dU suppression tests was identical with that found in vitamin-B12 deficiency, but the patients' serum-B12 concentrations were normal. These results suggest that nitrous oxide interferes with the function of vitamin B12. Nitrous oxide oxidises vitamin B12 in vitro, and probably also in vivo when premixed 50% nitrous oxide and 50% oxygen mixture ('Entonox') is given.