Intracranial EEG-fMRI analysis of focal epileptiform discharges in humans.

PURPOSE: Combining intracranial electroencephalography (iEEG) with functional magnetic resonance imaging (fMRI) is of interest in epilepsy studies as it would allow the detection of much smaller interictal epileptiform discharges than can be recorded using scalp EEG-fMRI. This may help elucidate the spatiotemporal mechanisms underlying the generation of interictal discharges. To our knowledge, iEEG-fMRI has never been performed at 3 Tesla (3T) in humans. We report our findings relating to spike-associated blood oxygen level-dependent (BOLD) signal changes in two subjects. METHODS: iEEG-fMRI at 3T was performed in two subjects. Twelve channels of iEEG were recorded from subdural strips implanted on the left posterior temporal and middle frontal lobes in a 20-year-old female with bilateral periventricular gray matter heterotopia. Twenty channels of iEEG were recorded bilaterally from two subdural strips laid anterior-posterior along mesial temporal surfaces in a 29-year-old woman with bilateral temporal seizures and mild left amygdalar enlargement on MRI. Functional MRI (fMRI) statistical maps were generated and thresholded at p = 0.01. KEY FINDINGS: No adverse events were noted. A total of 105 interictal discharges were recorded in the posterior middle temporal gyrus of Subject 1. In Subject 2, 478 discharges were recorded from both mesial temporal surfaces (n = 194 left, 284 right). The right and left discharges were modeled separately, as they were independent. Subject 1 showed spike-associated BOLD signal increases in the left superior temporal region, left middle frontal gyrus, and right parietal lobe. BOLD decreases were seen in the right frontal and parietal lobes. In Subject 2, BOLD signal increases were seen in both mesial temporal lobes, which when left and right spikes were modeled independently, were greater on the side of the discharge. In addition, striking BOLD signal decreases were observed in the thalamus and posterior cingulate gyrus. SIGNIFICANCE: iEEG-fMRI can be performed at 3T with low risk. Notably, runs of only 5 or 10 min of EEG-fMRI were performed as part of our implementation protocol, yet a significant number of epileptiform discharges were recorded, allowing meaningful analyses. With these studies, we have shown that deactivation can be seen in individual subjects with focal epileptiform discharges. These preliminary observations suggest a novel mechanism through which focal interictal discharges may have widespread cortical and subcortical influences.

Effect of endurance training on blood lactate clearance after maximal exercise.

The aim of this study was to measure serial changes in the rate of blood lactate clearance (gamma2) in response to sequential periods of training and detraining in four male triathletes aged 22-44 years. There were two major phases of training and taper, each lasting 4-5 weeks (training 1 = 5 weeks, taper 1 = 2 weeks, training 2 = 4 weeks and taper 2 = 2 weeks), in preparation for a triathlon competition. The training stimulus absorbed by each subject was carefully quantified from the duration and intensity of the training exercise. A serial weekly measure of each trainee's physical response to training was evaluated as the peak power, termed a 'criterion performance', developed by a subject during a 30 W x min(-1) ramp cycle ergometer test to exhaustion each week. During 30 min of recovery after this test, 13 samples of venous blood were drawn sequentially from a subject to measure the blood lactate recovery curve. The rate constant of blood lactate clearance was estimated by a non-linear least-squares regression technique. In addition, the concurrent time to peak lactate concentration and the peak lactate concentration were also estimated to help define changing lactate kinetics. The criterion performance generally declined throughout each period of incremental training and improved during each taper period, rising iteratively in this way to be clearly above baseline by the end of the second taper. The blood lactate clearance rate increased transiently in early training before declining from the middle of the first training period to the middle of the first taper; thereafter, gamma2 increased above baseline in each trainee throughout the remaining first taper and the major portion of the second training period, decreasing only in the final criterion performance test. The time to peak lactate declined from baseline throughout all phases of training and taper. Peak blood lactate increased in all subjects to the end of the first taper before declining by the end of the second training period, rising again to baseline levels during the second taper. The change in gamma2 was examined relative to the work rate achieved in cycle ergometry above an initial baseline score (deltaCP) and against concurrent peak blood lactate. There was a clear upward shift in gamma2 above baseline throughout the first and second training and taper in two subjects; this was less clear in the remaining two subjects, each of whom had a lower deltaCP. We conclude that this indicates improved lactate clearance, manifest by the change in gamma2 induced by endurance training.

Accelerated nodulosis during methotrexate therapy for juvenile rheumatoid arthritis.

We describe two patients with rheumatoid factor-positive, polyarticular-onset juvenile rheumatoid arthritis in whom accelerated nodulosis developed during methotrexate therapy. Although they had only a few nodules at diagnosis, the nodules increased in number and size 3 to 4 months after the start of methotrexate therapy in both patients. The nodules regressed after withdrawal of methotrexate therapy in one patient and were arrested with the addition of hydroxychloroquine in the other. Physicians treating patients with methotrexate for juvenile rheumatoid arthritis must be aware of this extraarticular side effect.

Blood group glycolipids as epithelial cell receptors for Candida albicans.

The role of glycosphingolipids as possible epithelial cell receptors for Candida albicans was examined by investigating the binding of biotinylated yeasts to lipids extracted from human buccal epithelial cells and separated on thin-layer chromatograms. Binding was visualized by the addition of 125I-streptavidin followed by autoradiography. Five C. albicans strains thought from earlier work to have a requirement for fucose-containing receptors all bound to the same three components in the lipid extract. A parallel chromatogram overlaid with biotinylated Ulex europaeus lectin, which is a fucose-binding lectin with a specificity for the H blood group antigen, showed that two of these glycosphingolipids carried this antigenic determinant. Preparations of crude and purified adhesin (a protein with a size of 15.7 kDa which lacked cysteine residues) from one of the strains also bound to these same two components. The third glycosphingolipid, which bound whole cells but neither preparation of adhesin, was recognized by Helix pomatia lectin, indicating that it contained N-acetylgalactosamine, possibly in the form of the A blood group antigen. Overlay assays with a sixth strain of C. albicans (GDH 2023) revealed a completely different binding pattern of four receptors, each of which contained N-acetylglucosamine. These results confirm earlier predictions about the receptor specificity of the strains made on the basis of adhesion inhibition studies and indicate that blood group antigens can act as epithelial cell receptors for C. albicans.

Statistical evidence consistent with two lactate turnpoints during ramp exercise.

A number of studies have identified the existence of two ventilation thresholds during ramp or incremental exercise to exhaustion on the cycle ergometer. This study was undertaken to investigate whether two threshold turnpoints could be identified in blood lactate concentration data collected at such times. Five trained athletes provided serial blood samples on several occasions each during a 3-month period of training. Blood lactate concentration was analysed by fitting models with no, one or two turnpoints. Ordinary residuals from the first two models were often found to exhibit an oscillatory behaviour consistent with the existence of two turnpoints in lactate concentration. A comparative analysis of goodness of fit of these models revealed that the model with two turnpoints was significantly better than either of the simpler models. This suggests that two transitions exist, which divide the time domain for blood lactate concentration in ramp exercise into three regions. These two transitions may correspond to the two ventilation thresholds.

The clearance rate of exercise-elevated blood lactate following physical training.

In this paper, previous studies regarding the effect of physical training on the disappearance rate of blood La during recovery after strenuous exercise have been briefly summarized. The results of our own recent study of this problem have also been added. It may be concluded that there is some evidence for an improved lactate metabolic clearance rate resulting from physical training in human subjects, when the degradation rate is estimated from serial blood samples taken during a standard ramp ergometer test to exhaustion during each week of a training/detraining sequence. This beneficial effect of training, however, may also be influenced by the initial physical status of the subject and the nature of the training program.

Exercise-induced hyperammonemia: peripheral and central effects.

The intent of this paper is to review the recent literature on exercise-induced hyperammonemia (EIH) and to compare the current interpretations of ammonia accumulation during exercise with the recognized clinical symptoms of progressive ammonia toxicity. In doing so, we will speculate on possible exercise-induced symptoms of CNS dysfunction which could result from elevated ammonia during intense short-duration or prolonged exercise. Ammonia is a ubiquitous metabolic product producing multiple effects on physiological and biochemical systems. Its concentration in several body compartments is elevated during exercise, predominantly by increased activity of the purine nucleotide cycle (PNC) in skeletal muscle. Depending on the intensity and duration of exercise, muscle ammonia may be elevated to the extent that it leaks (diffuses) from muscle to blood, and thereby can be carried to other organs. The direction of movement of ammonia or the ammonium ion is dependent on concentration and pH gradients between tissues. In this manner, ammonia can also cross the blood-brain barrier (BBB), although the rate of diffusion of ammonia from blood to brain during exercise is unknown. It seems reasonable to assume that exhaustive exercise may induce a state of acute ammonia toxicity which, although transient and reversible relative to disease states, may be severe enough in critical regions of the CNS to affect continuing coordinated activity. Regional differences in brain ammonia content, detoxification capacity, and specific sensitivity may account for the variability of precipitating factors and latency of response in CNS-mediated dysfunction arising from an exercise stimulus, e. g., motor incoordination, ataxia, stupor. There have been numerous suggestions that elevated ammonia is associated with, or perhaps is responsible for, exercise fatigue, although evidence for this relies extensively on temporal relationships. Fatigue may become manifest both as a peripheral organ or central nervous system phenomenon, or combination of both. Thus, we must examine the sequential or concomitant changes in ammonia concentration occurring in the periphery, the central nervous system (CNS), and the cerebrospinal fluid (CSF) induced by any effector, not only exercise, to interpret and rationalize the diverse physical, physiological, biochemical, and clinical symptoms produced by hyperammonemic states. Since more is known about elevated brain ammonia during other diverse conditions such as disease states, chemically induced convulsion, and hyperbaric hyperoxia, some of these relevant data are discussed.

Occurrence of Kawasaki disease and systemic lupus erythematosus in a single patient.

A 5-year-old girl who developed systemic lupus erythematosus 3 1/2 years after having had Kawasaki disease was found to be homozygous at both class I and class II MHC loci. This homozygosity suggests that she may also be homozygous for an MHC or non-MHC linked gene that could allow for the appearance of 2 diseases with similar immunoregulatory abnormalities, as occurs in the MRL/1pr/1pr mouse model. Although this is the first report of the occurrence of a second immunologic disorder in a patient with a history of Kawasaki disease, North American children who developed Kawasaki disease early in life are only now reaching the age when other inflammatory disorders become relatively common. Therefore, this group of children will have to be closely observed for the development of other inflammatory disorders.

Extreme ultraviolet reflectance degradation of aluminum and silicon from surface oxidation.

We have performed in situ oxide contamination and XUV reflectance vs angle of incidence studies on fresh aluminum and silicon films evaporated in an ultrahigh vacuum system (base pressure 2 x 10(-10)Torr). Our ellipsometric measurements indicate that a surface monolayer of oxide forms on aluminum (1 h at 2 x10(-8) Torr oxygen) and silicon (1 h at 10-(7) -Torr oxygen). The monolayer formation time is inversely proportional to oxygen pressure. Our reflectance vs angle of incidence measurements at 58.4-nm wavelength indicate that unoxidized aluminum and silicon coatings can be used as multifacet retroreflectors with net retroreflectances in excess of 75% for aluminum and 50% for silicon.

Idiopathic periosteal hyperostosis with dysproteinemia (Goldbloom's syndrome): case report and review of the literature.

Idiopathic subperiosteal new bone formation is uncommon in childhood. We report a case of diffuse periostitis in association with hypergammaglobulinemia and hypoalbuminemia in a 12-year-old boy. In 1966, 2 cases of idiopathic periosteal hyperostosis with accompanying dysproteinemia were documented. This report serves as a review of this unique and perplexing problem in clinical diagnosis.