Listeria Meningitis Complicating Alemtuzumab Treatment in Multiple Sclerosis—Report of Two Cases

Alemtuzumab, a humanized monoclonal antibody targeting the surface molecule CD52, leads to a rapid depletion of immune cells in the innate and adaptive immune system. In phase 2 and 3 trials in multiple sclerosis (MS), infections have been reported more frequently in alemtuzumab than in interferon beta treated patients. Here we report two patients treated with alemtuzumab for MS developing Listeria meningitis few days after the first infusion cycle. Both patients recovered completely after prompt diagnosis and adequate treatment. Physicians and patients should be aware of this serious, but treatable complication.     

On the capacity of the rat intestine to excrete lithium ions at therapeutic and toxic plasma lithium concentrations

Lithium (Li) excretion into the intestinal lumen was quantitated in rats in situ by use of a pendular perfusion technique. Male Sprague-Dawley rats were injected daily (7-10 days) i.p. with 1, 3, and 6 mmol LiCl per kg body weight (n = 9-12). Jejunal as well as ileal and colonic segments were perfused with isotonic saline containing 3H-PEG-4000. Perfusate samples were taken after 0, 5, 10, 20, and 60 min. At the highest dose toxic symptoms were observed. At 6 mmol Li per kg the plasma Li concentrations were higher than those linearly extrapolated from the lower-dose groups, which may be due to inappropriate renal excretion. The Li concentration in the perfusate increased linearly over time and was not significantly different between jejunal and colonic segments. The same ratio between the Li concentration in the plasma and in the luminal perfusate was observed in all groups. Intestinal Li excretion is not impaired by high plasma concentrations. The intestinal capacity to excrete Li is considerable: 45 cm of jejunum is able to excrete the intire plasma Li content in 30-40 min, when Li is not resupplemented from intracellular stores. The renal clearance of lithium (Li) decreases when toxic Li plasma concentrations are reached. Therefore, if it were possible to trap Li in the intestinal lumen, this excretion route might be of therapeutic interest in cases of Li intoxication with impaired renal Li-excretion.     

Non-Stationary response of a vehicle obtained from a series of stationary responses

Ride characteristics of a vehicle moving on a rough ground with changing travel velocity are analyzed in this paper. The solution is difficult due to the non-stationary characteristics of the problem. Hence a new technique has been proposed to overcome this difficulty. This new technique is employed in the analysis of ride characteristics of a vehicle with changing velocity in the time/frequency domain. It is found that the proposed technique gives successful results in modelling non-stationary responses in terms of a series of stationary responses.     

Scale-up studies for stable,long-term indoor and outdoor production of hydrogen by immobilized Rhodobacter capsulatus

Photofermentative hydrogen production by immobilized Rhodobacter capsulatus YO3 was carried out in a novel photobioreactor in sequential batch mode under indoor and outdoor conditions. Long-term H₂ production was realized in a 1.4 L photobioreactor for 64 days using Rhodobacter capsulatus YO3 immobilized with 4% (w/v) agar on 5 mM sucrose and 4 mM glutamate. The highest hydrogen yield (19 mol H₂/mol sucrose) and hydrogen productivity (0.73 mmol H₂ L^?1 h^?1) were achieved indoors on 5 mM sucrose. The effect of initial sucrose concentration (5 mM, 10 mM, and 20 mM) on hydrogen production was also investigated. Sustained hydrogen production was carried out under natural, outdoor conditions as well. For the outdoor experiments, the highest hydrogen productivity and yield were obtained as 0.87 ± 0.06 mmol H₂ L^?1 h^?1 and 6.1 ± 0.2 mol H₂/mol sucrose, respectively on 10 mM sucrose. Furthermore, this system prevented sudden pH drops and fluctuations caused by the utilization of sucrose throughout the process. These results demonstrate that a proper immobilization setup can lead to long-term efficient and robust hydrogen production even under naturally varying conditions.     

Brain-Specific Cytoskeletal Damage Markers in Cerebrospinal Fluid: Is There a Common Pattern between Amyotrophic Lateral Sclerosis and Primary Progressive Multiple Sclerosis?

Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs.     

Investigation of factors affecting caking tendency of calcium ammonium nitrate fertilizer and coating experiments

Caking of fertilizers is an important problem both to manufacturers and users. Manufacturers must recycle the caked fertilizer to the process resulting in an extra cost and users may have difficulties during the application of the fertilizer to the soil. In the first part of this study major factors which influence caking of a commercial grade calcium ammonium nitrate (CAN) fertilizer were investigated with a laboratory caking apparatus kept in a controlled atmosphere. It was observed that the caking tendency of CAN fertilizer increases almost linearly with pressure exerted on the fertilizer and with moisture content of the fertilizer at a temperature of 35 °C. The results indicate that the phase transition of ammonium nitrate between crystalline forms IV and III plays a significant role in caking of CAN since caking tendency is greatly reduced below the phase transition temperature which occurs at about 32 °C. In the second part of the study, the effectiveness of some coating materials to reduce the caking tendency of CAN fertilizer were tested. Among the materials tested, kieselguhr gave the most satisfactory result under the experimental conditions employed.     

A Study of Prosthetic Heart Valve Sounds

In this paper a new mechanism is proposed for the generation of phonocardiogram (PCG) sounds from implanted mechanical prosthetic heart valves. The structures in the chest, the heart, its partitions, and major vessels, constitute a frequency selective system excited by the rapidly decelerating valve occluder. It is shown that the source, the rapidly decelerating valve, has a wide and flat power spectrum and hence is an impulsive excitation that couples energy to the resonance modes specified by the structures in the chest. Consequently, the PCG signal is composed of decaying sinusoids. The parameters of the decaying sinusoids are estimated, and it is observed that the power spectra of the PCG signals have two dominant peaks in the frequency band of 200-500 Hz. The energy coupled to these two modes depends on the state of the valve. With thrombus the decelerating occluder slows down and becomes a broader pulse concentrating the energy to the lower resonance mode. This is verified by experiments on 30 patients during postoperative time course. However, no significant change in the resonance frequencies are observed which is an evidence for their anatomical and not valvular dependence.     

Genetic algorithm with local search for the unrelated parallel machine scheduling problem with sequence-dependent set-up times

In this paper, a genetic algorithm (GA) with local search is proposed for the unrelated parallel machine scheduling problem with the objective of minimising the maximum completion time (makespan). We propose a simple chromosome structure consisting of random key numbers in a hybrid genetic-local search algorithm. Random key numbers are frequently used in GAs but create additional difficulties when hybrid factors are implemented in a local search. The best chromosome of each generation is improved using a local search during the algorithm, but the better job sequence (which might appear during the local search operation) must be adapted to the chromosome that will be used in each successive generation. Determining the genes (and the data in the genes) that would be exchanged is the challenge of using random numbers. We have developed an algorithm that satisfies the adaptation of local search results into the GAs with a minimum relocation operation of the genes’ random key numbers – this is the main contribution of the paper. A new hybrid approach is tested on a set of problems taken from the literature, and the computational results validate the effectiveness of the proposed algorithm.