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Biomedical subjects

Andrew A Marino

Publications and source records attributed to Andrew A Marino.

13 recordsLinked to original sources

Detection of nonlinear event-related potentials.

The methods used to evaluate event-related potentials (ERPs) are generally insensitive to nonlinear responses. Our goal was to show that nonlinear ERPs could be detected using recurrence analysis (RA). When fixed-phase sine signals were added to baseline electroencephalograms (EEGs), the added linear determinism was detected by signal averaging, as expected, and by RA. However, when nonlinear determinism was simulated by adding either random-phase sine or Lorenz signals, the added signals were detected only by RA. Auditory evoked potentials (AEPs) were studied in five subjects using RA. We detected not only the characteristic linear effects caused by onset and offset of the sound, but also nonlinear AEPs not previously reported; they occurred at 473-661 ms after onset, and 282-602 ms after offset, depending on the subject. In five other subjects we found nonlinear magnetosensory evoked potentials; they occurred at 209-354 ms after field onset, depending on the subject. RA was less sensitive than time averaging for detecting linear ERPs, but had the advantage of being able to detect nonlinear ERPs.

Acoustic Stimulation↗

Assessment of immunologic mechanisms for flare reactions to Synvisc.

Intraarticular injection of Synvisc for treatment of knee pain sometimes results in an acute local reaction (flare). We tested the hypothesis that the flare was a Type-1 hypersensitivity reaction as manifested by the presence of Synvisc antibodies in the synovial fluid and serum and by an increase in the concentration of the mast-cell enzyme tryptase in the synovial fluid. Our second objective was to determine whether the ratio of CD4+ to CD8+ lymphocytes in the synovial fluid was increased, as would be expected in a Type-4 hypersensitivity reaction. The study population was a prospective, consecutive series of 16 patients who had a flare, and 20 control patients. We found no differences in product-specific antibodies in the synovial fluid or serum between patients with flares and patients without flares. The mean tryptase level in the synovial fluid of patients with flares, 3.8 +/- 0.8 microg/L, was not different from the corresponding level in the control patients. The CD4+/CD8+ ratio in the synovial fluid was more than eight times greater in patients with flares. Flares that sometimes occur after treatment with Synvisc are probably not Type-1 (antibody-mediated) hypersensitivity reactions, but may be Type-4 (cell-mediated) hypersensitivity reactions.

Aged↗

External suction drainage in primary total joint arthroplasties.

We compared a novel external suction drainage (ESD) system with a conventional internal suction drainage (ISD) system in patients undergoing primary total hip or knee arthroplasties. Forty-two consecutive patients were studied: 22 who received an ISD system and 20 who received the ESD system. Drainage volume was measured, standardized questionnaires were used to assess patient comfort and response to drain removal, and number of complications were recorded. Significantly less drainage, less pain, and fewer complications occurred in patients treated with the ESD system (P<.05 for each endpoint). Results showed that ESD has advantages over ISD in primary total hip and knee arthroplasties.

Arthroplasty, Replacement, Hip↗

Effect of low-frequency magnetic fields on brain electrical activity in human subjects.

OBJECTIVE: To measure the response rate of normal human subjects to a low-strength, low-frequency magnetic field (MF), using nonlinear quantitative analysis of the electroencephalogram (EEG). METHODS: Eight subjects were exposed to a series of trials, each consisting of the application of the MF (1 G, 60 Hz) for 2 s followed by a field-free period of 5 s, and the EEG was analyzed statistically using phase-space methods to assess whether the subject detected the MF. RESULTS: Each subject exhibited statistically significant changes in the EEG during presentation of the MF, as evidenced by increases in percent determinism and percent recurrence, two different measures of deterministic structure in the recorded signal, thereby indicating that the MF had been detected. CONCLUSIONS: The 100% response rate manifested by the study group suggested that the ability to detect low-strength, low-frequency MFs is a common property of the human nervous system.

Adult↗

Increased intercellular communication through gap junctions may contribute to progression of osteoarthritis.

Our aim was to support the hypothesis of a specific association between gap junctions in synovial tissue and the presence of osteoarthritis, as evidenced by differences between osteoarthritis and non-osteoarthritis synovia in the number of gap junctions, the amount of gap-junction protein, and the amount of enzymatic activity produced through a pathway mediated by gap-junction intercellular communication. An average of 4.41 gap junctions were found per 100 cells counted in the osteoarthritis synovia, compared with 1.00 in the controls. The amount of the gap-junction protein connexin 43 in synovial lining cells was approximately 50% greater in patients with osteoarthritis. Synovial lining cells from patients with osteoarthritis produced matrix metalloproteinases constitutively and, at higher levels, in response to stimulation by interleukin-1 beta. In both cases, intercellular communication through gap junctions was shown to be critical to the ability of the cells to secrete matrix metalloproteinases. Overall, the results indicated that gap junctions between synovial lining cells were altered significantly in patients with osteoarthritis, as a consequence of the disease process or as part of the causal chain. In either case, gap junctions seem to be a rational therapeutic target.

Aged↗

Consistent magnetic-field induced dynamical changes in rabbit brain activity detected by recurrence quantification analysis.

The reports dealing with the effects of electromagnetic fields (EMFs) on brain electrical activity have been inconsistent. We suspected that the use of linear methods and models accounted for some of the variability, and we explored the issue by using a novel approach to study the effects of EMFs on the electroencephalogram (EEG) from rabbits. The EEG was embedded in phase space and local recurrence plots were calculated and quantified to permit comparisons between exposed and control epochs from individual animals. Statistically significant alterations in brain activity were observed in each animal (n=10) when it was exposed to 2.5 G, 60 Hz, as assessed using each of two recurrence-plot quantifiers. Each result was replicated; a positive-control procedure ruled out the possibility that the effect of the field was a product of the method of analysis. Measurements performed while the rabbits were under anesthesia suggested that the effect was mediated by N-methyl-D-aspartate and/or alpha(2)-adrenoceptors. No differences were found between exposed and control epochs in any animal when the experiment was repeated after the rabbits had been killed, indicating that a putative interaction between the field and the EEG electrodes could not account for the observed effects. We conclude that EMF transduction resulting in changes in brain electrical activity could be demonstrated consistently using a nonlinear method of analysis.

Animals↗

Extracellular currents alter gap junction intercellular communication in synovial fibroblasts.

We studied the effect of extremely low frequency (ELF) currents on gap junction intercellular communication (GJIC) mediated by connexin43 protein. Confluent monolayers of synovial fibroblasts (HIG-82) and neuroblastoma cells (5Y) were exposed in bath solution to 0-75 mA/m(2) (0-56 mV/m), 60 Hz. Single channel conductance, cell membrane current-voltage (I-V) curves, and Ca(2+) influx were measured using the nystatin single and double patch methods. The conductances of the closed and open states of the gap junction channel in HIG-82 cells were each significantly reduced (by 0.76 and 0.39 pA, respectively) in cells exposed to 20 mA/m(2). Current densities as low as 10 mA/m(2) significantly increased Ca(2+) influx in HIG-82 cells. No effects were seen in 5Y cells. The I-V curves of the plasma membranes of both types of cells were independent of 60 Hz electric fields and current densities, 0-75 mA/m(2), indicating that the effect of the 60 Hz fields on GJIC in HIG-82 cells was not mediated by a change in membrane potential. We conclude that ELF electric fields can alter GJIC in synovial cells via a mechanism that does not depend on changes in membrane potential, but may depend on Ca(2+) influx. The results open the possibility that GJIC mediated responses in synovial cells, such as for example, their secretory responses to proinflammatory cytokines, could be antagonized by the application of ELF electric fields.

Animals↗

Nonlinear changes in brain electrical activity due to cell phone radiation.

We studied the effect of an electromagnetic field from a cellular telephone on brain electrical activity, using a novel analytical method based on a nonlinear model. The electroencephalogram (EEG) from rabbits was embedded in phase space and local recurrence plots were calculated and quantified using recurrence quantitation analysis to permit statistical comparisons between filtered segments of exposed and control epochs from individual rabbits. When the rabbits were exposed to the radiation from a standard cellular telephone (800 MHz band, 600 mW maximum radiated power) under conditions that simulated normal human use, the EEG was significantly affected in nine of ten animals studied. The effect occurred beginning about 100 ms after initiation of application of the field and lasted approximately 300 ms. In each case, the fields increased the randomness in the EEG. A control procedure ruled out the possibility that the observations were a product of the method of analysis. No differences were found between exposed and control epochs in any animal when the experiment was repeated after the rabbits had been sacrificed, indicating that absorption of radiation by the EEG electrodes could not account for the observed effect. No effect was seen when deposition of energy in the brain was minimized by repositioning the radiating antenna from the head to the chest, showing that the type of tissue that absorbed the energy determined the observed changes in the EEG. We conclude that, in normal use, the fields from a standard cellular telephone can alter brain function as a consequence of absorption of energy by the brain.

Action Potentials↗

Localization of electroreceptive function in rabbits.

The detection process by which animals react to the presence of electromagnetic fields (EMFs) may be a form of sensory transduction. However, the anatomic location of signal transduction in most species is unknown. Attempts to solve this problem by applying local EMFs and registering the resulting changes in the electroencephalogram (EEG) have not succeeded because of the nonstationarity of the EEG and the insensitivity of linear methods of analysis. We approached the problem of localizing electroreception in rabbits by using recurrence quantification analysis (RQA), a novel method of nonlinear analysis designed to detect small deterministic changes in a larger signal irrespective of considerations involving stationarity. When 2.5 G, 60 Hz was applied to the entire body, increased determinism in the EEG was found in all 10 animals studied, as evidenced by statistically significant increases in two RQA quantifiers. A similar result occurred when the field was applied only to the front half of each animal, but no effect on the EEG was seen when the field was applied only to the back half. When the field was localized to the head, the effect on the determinism in the EEG was again seen. When the field was further localized to the eye, the effect did not occur. Overall, the results indicated that detection of the field occurred in cells or extracellular structures in the head, probably the brain, although the methods used did not have the resolution to discriminate between specific brain structures. Thus, our results showed that the presence of transient deterministic brain states induced by an EMF signal could be documented using dynamical analysis, thereby allowing us to infer the approximate anatomic location of the signal's transduction.

Animals↗

Consistent magnetic-field induced dynamical changes in rabbit brain activity detected by recurrence quantification analysis.

The reports dealing with the effects of electromagnetic fields (EMFs) on brain electrical activity have been inconsistent. We suspected that the use of linear methods and models accounted for some of the variability, and we explored the issue by using a novel approach to study the effects of EMFs on the electroencephalogram (EEG) from rabbits. The EEG was embedded in phase space and local recurrence plots were calculated and quantified to permit comparisons between exposed and control epochs from individual animals. Statistically significant alterations in brain activity were observed in each animal (n=10) when it was exposed to 2.5 G, 60 Hz, as assessed using each of two recurrence-plot quantifiers. Each result was replicated; a positive-control procedure ruled out the possibility that the effect of the field was a product of the method of analysis. Measurements performed while the rabbits were under anesthesia suggested that the effect was mediated by N-methyl-D-aspartate and/or alpha(2)-adrenoceptors. No differences were found between exposed and control epochs in any animal when the experiment was repeated after the rabbits had been killed, indicating that a putative interaction between the field and the EEG electrodes could not account for the observed effects. We conclude that EMF transduction resulting in changes in brain electrical activity could be demonstrated consistently using a nonlinear method of analysis.

Algorithms↗

IL-1beta-induced production of metalloproteinases by synovial cells depends on gap junction conductance.

Synovial cells can form networks connected by gap junctions. The purpose of this study was to obtain evidence for a necessary role of gap junction intercellular communication in protein secretion by synovial cells. We developed a novel assay to measure the enzymatic activity of metalloproteinases (MMPs) produced by synovial cells in response to interleukin-1beta (IL-1beta) and employed the assay to explore the biological function of gap junctions. IL-1beta produced a dose-dependent increase in MMP activity that was blocked by exposure to the gap junction inhibitors 18alpha-glycyrrhetinic acid and octanol for as few as 50 min. The inhibitors produced an immediate and marked reduction in intercellular communication, as assessed by transient current analysis using the nystatin perforated-patch method. These observations suggest that communication through gap junctions early in IL-1beta signal transduction is critical to the process of cytokine-regulated secretion of MMPs by synovial cells.

Animals↗