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T Walczak

Publications and source records attributed to T Walczak.

At least 19 recordsLinked to original sources

Epidemiological and medical aspects of epilepsy in the elderly.

Both the incidence and prevalence of epilepsy are high among the elderly. Cerebrovascular disease is the most common underlying cause, although as many as 25-40% of new epilepsy cases in the elderly have no obvious underlying etiology. Status epilepticus appears to occur more frequently in individuals greater than 60 years, and the morbidity and mortality of status epilepticus are significantly greater in this age group. Elderly patients with seizures, particularly complex partial seizures, present differently than younger adults, which can lead to misdiagnosis. Post-ictal confusion may last as long as 1-2 weeks in an elderly patient, as opposed to minutes in younger individuals. Adverse events are similar in symptomatology, but are more common in elderly patients and occur at lower doses and plasma drug concentrations. Neuropsychiatric disorders, such as depression and anxiety, are common in elderly patients with epilepsy, although often under-diagnosed and inadequately treated. The risk of osteoporosis is high among elderly women taking antiepileptic drugs, which underscores the importance of assessing bone health and treatment in this group. Management of the older patient with epilepsy requires an understanding of the etiologies and the medical and psychological aspects unique to this age group.

Aged↗

Development and evaluation of biocompatible films of polytetrafluoroethylene polymers holding lithium phthalocyanine crystals for their use in EPR oximetry.

Electron paramagnetic resonance (EPR) oximetry is a powerful technology that allows the monitoring of oxygenation in tissues. The measurement of tissue oxygenation can be achieved using lithium phthalocyanine (LiPc) crystals as oxygen reporters. In order to have biocompatibility for the sensing system and to assure long-term stability in the responsiveness of the system, we developed films of Teflon AF 2400 with embedded LiPc crystals. These systems can be used as retrievable inserts or parts of an implantable resonator or catheter. Atomic force microscopy studies revealed that the surface of the films was regular and planar. The response to oxygen of the sensor (EPR linewidth as a function of pO(2)) remained unchanged after implantation in mice, and was not affected by sterilization or irradiation. The use of resonators, holding LiPc embedded in Teflon AF 2400, implanted in the gastrocnemius muscle of rabbits allowed the monitoring of oxygen during several weeks. Several assays also demonstrated the biocompatibility of the system: (1) no hemolytic effect was noted; (2) no toxicity was found using the systemic injection test of extracts; (3) histological analysis in rabbit muscle in which the films were implanted for 1 week or 3 months was similar to standard polyethylene biocompatible devices. These advanced oxygen sensors are promising tools for future pre-clinical and clinical developments of EPR oximetry. These developments can be applied for other applications of biosensors where there is a need for oxygen permeable membranes.

Absorption↗

EPR spectrometer for clinical applications.

This article describes an EPR spectrometer specifically designed and constructed for EPR spectroscopy in humans. The spectrometer is based on a permanent magnet, suitable for measurements at 1200 MHz. The magnet has a full 50 cm gap between the poles, which facilitates accurate and comfortable placement of the subject for the EPR measurement at any location on the human body. The bridge includes features to facilitate clinical operations, including an indicator for phasing of the reference arm and a 2 level RF amplifier. Resonators with holders for each type and site of measurement have been developed that comfortably position the resonator and the patient and prevent artifacts due to motion. The initial applications for which the spectrometer has been designed are for oximetry using loops on the surface, oximetry using implanted resonators for measuring deep sites, and measurements in the teeth for determination of exposures to clinically significant doses of ionizing radiation.

Electron Spin Resonance Spectroscopy↗

How long does it take for partial epilepsy to become intractable?

BACKGROUND: Much remains unknown about the natural history of intractable localization-related epilepsy, including how long it typically takes before intractability becomes evident. This information could guide the design of future studies, resolve certain discrepancies in the literature, and provide more accurate information about long-term prognosis. METHODS: Individuals evaluated for resective surgery for refractory localization-related epilepsy were prospectively identified at the time of initial surgical evaluation at seven surgical centers (between 1996 and 2001). The latency time between onset of epilepsy and failure of second medication and history of remission (>/=1 year seizure-free) before surgical evaluation were examined with respect to age at onset, hippocampal atrophy, febrile seizures, and surgical site. RESULTS: In the 333 patients included in the analysis, latency time was 9.1 years (range 0 to 48) and 26% reported a prior remission before surgery. A prior remission of >/=5 years was reported by 8.5% of study participants. Younger age at onset was strongly associated with longer latency time (p < 0.0001) and higher probability of past remission (p < 0.0001). In multivariable analyses, age at onset remained as the most important explanatory variable of both latency time and prior remission. CONCLUSIONS: A substantial proportion of localization-related epilepsy may not become clearly intractable for many years after onset. This is especially true of epilepsy of childhood and early adolescent onset. If prospective studies confirm these findings and the underlying mechanisms behind these associations become understood, this raises the possibility of considering interventions that might interrupt such a process and some day prevent some forms of epilepsy from becoming intractable.

Adolescent↗

Electronically tunable surface-coil-type resonator for L-band EPR spectroscopy.

The automatic frequency control (AFC) circuit in conventional electron paramagnetic resonance (EPR) spectrometers automatically tunes the microwave source to the resonance frequency of the resonator. The circuit works satisfactorily for samples stable enough that the geometric relations in the resonance structure do not change in a significant way. When EPR signals are measured during in vivo experiments with small rodents, however, the distance between the signal source and the surface-coil detector can change rapidly. When a conventional AFC circuit keeps the oscillator tuned to the resonator under those conditions, the resultant frequency change may exceed +/-5 MHz and markedly shift the position of the EPR signal. Such a shift results in unacceptable effects on the spectra, especially when the experimenter is dealing with narrow EPR lines. The animal movement also causes a mismatching of the resonator and the 50-ohm transmission line. Direct results of this mismatching are increased noise; shifts in the position of the baseline; and a high probability of overdriving the signal preamplifier with consequent loss of the EPR signal. We therefore designed, built, and tested a new surface-coil resonator using varactor diodes for tuning the resonance frequency to the fixed frequency oscillator and for capacitive matching of the resonator to the 50-ohm transmission line. The performance of the automatic matching system was tested in vivo by measuring EPR spectra of lithium phthalocyanine implanted in rats. Stability and sensitivity of the spectrometer were evaluated by measuring EPR spectra with and without the use of the automatic matching system. The overall experimental performance of the spectrometer was found to significantly improve during in vivo experiments using the automatic matching system. Excellent matching between the 50-ohm transmission line and the resonator was maintained under all experimental circumstances that were tested. This should allow us now to carry out experiments that previously were not possible.

Animals↗

Kinetics of chromium(V) formation and reduction in fronds of the duckweed Spirodela polyrhiza--a low frequency EPR study.

The uptake of chromate by the duckweed Spirodela polyrhiza was investigated with atomic absorption spectroscopy and the reduction of Cr(VI) to Cr(V) was measured using low frequency EPR spectroscopy. The biphasic kinetics of the uptake was fitted to parameters of a proposed kinetic model. Another model was developed to simulate chromate reduction. The first step of chromate reduction was found to be much faster than the uptake of Cr(VI) from the free space. Most probably, this step occurs already in the cell wall or on the cell membrane surface. Further reduction of Cr(V) to Cr(III) was estimated to be slower. The disappearance of the Cr(V) signal, following transfer of the plants into a Cr-free solution, lasted several tens of hours; the kinetics was mono- or biexponential depending on the length of Cr loading. The rate constants for Cr reduction in living plants were determined for the first time.

Chromium↗

Small particles of fusinite and carbohydrate chars coated with aqueous soluble polymers: preparation and applications for in vivo EPR oximetry.

The development of oxygen-sensitive paramagnetic materials is being pursued actively because of their potential applications in in vivo EPR oximetry. Among these materials, several charcoals and carbohydrate chars are of special interest because of their desirable EPR properties: high sensitivity of the EPR linewidth to the partial pressure of oxygen, simple EPR spectra, and high spin density. Their potential use in humans, however, is limited by the need to demonstrate that they will not lead to deleterious effects. A strategy was used to optimize the biocompatibility of the oxygen-sensitive materials by decreasing the size of the particles and coating them with suspending or surfactive agents such as arabic gum, poloxamer (Pluriol 6800), and polyvinylpyrrolidone. The coated particles of a carbohydrate char and fusinite were characterized in vitro for their size, stability, and pO2 sensitivity. The feasibility of performing pO2 measurement was examined in vivo by inducing ischemia in the gastrocnemius muscle of mice. The use of arabic gum for coating the fusinite particles preserved the pO2 sensitivity in vivo, whereas the other surfactive agents led to a loss of the pO2 sensitivity in vivo. Small particles of fusinite coated by arabic gum and intravenously administered to mice accumulated in the liver, whereas the uncoated fusinite was toxic when injected intravenously due to the large size and aggregation of the particles. Histological studies performed up to 6 months after the injection in muscles of mice did not indicate any toxicity from the materials used in the present study.

Animals↗

Developing in vivo EPR oximetry for clinical use.

This paper describes the rationale for carrying out electron paramagnetic resonance (EPR) oximetry studies in human subjects in the clinical setting and the potential approaches and specific steps needed to make such studies feasible and useful. While the approach is described specifically for EPR oximetry, many of the principles may apply to the initial clinical uses of other techniques. The suggested operational approach is to have the initial applications occur in as clinically useful and simple a manner as possible, with the expectation that once the technique is introduced and accepted in the clinical setting, that more complex and/or more technically difficult applications will be able to be developed. The initial approach will be based on EPR spectroscopy at 1.2 GHz focusing on applications for which in vivo EPR provides a clearly useful approach to important clinical problems for which currently there is no good alternative method. The EPR measurements can be carried out non-invasively by measurements within 10 mm of the surface after the placement of the paramagnetic material at the site of interest, or by the placement of a needle/catheter in the site of interest for the required time period. The suggested initial clinical applications are guiding therapy for individual patients with tumors or vascular disease, by direct measurements of tissue pO2.

Animals↗

Multivariable prediction of seizure outcome one year after resective epilepsy surgery: development of a model with independent validation.

PURPOSE: To identify predictors of seizure-outcome after epilepsy surgery and validate the findings in an independent series of patients. To use the results to develop a predictive model. METHODS: Sequential patients undergoing resective surgery for medically intractable epilepsy were identified at Yale New Haven Hospital (1987-1990, group 1) and Columbia Presbyterian Hospital (1991-1994, group 2). Information about seizure outcome and predictors of outcome was obtained from medical chart review. Good seizure-outcome was defined as having been seizure-free for one year beginning with discharge from the hospital. Multiple logistic regression was used to develop a model of predictors in group 1. It was then validated in group 2. RESULTS: There were 133 patients in group 1 and 81 in group 2. In a multivariable analysis, independent predictors of outcome in group 1 were presence of mesial temporal sclerosis based on postsurgical pathological analysis (MTS) (relative risk (RR) = 1.47), having a known underlying etiology (RR = 1.32), and partial seizures only (RR = 1.17). In group 2, the findings for each factor were similar to those in group 1: MTS, RR = 1.49; etiology, RR = 1.32; and partial seizures, RR = 1.24. Used in combination, these three factors can identify patients with nearly a 100% chance of being seizure-free (all three factors present) versus less than a 50% chance (none of the three factors present). CONCLUSIONS: With independent validation of the findings, we can be reasonably certain that the three factors identified in this analysis are meaningful and generalizable predictors of seizure outcome following epilepsy surgery. Use of predictive models should be considered in future studies to convert study results into clinically relevant statements about a particular patient's likelihood of surgical success.

Adolescent↗

Low-frequency EPR study of chromium(V) formation from chromium(VI) in living plants.

The reduction of Cr(VI) by green algae and higher plants was investigated using a low-frequency EPR spectrometer equipped with an extended loop gap resonator. Incubation of algae (Spirogyra and Mougeotia) with Cr(VI) generated both Cr(V) and Cr(III). The maximum Cr(V) signal was observed in about 10 minutes. Incubation of Cr(VI) with oat, soybean, and garlic generated Cr(V). The maximum Cr(V) peak appeared after more than 10 hours of incubation, and Cr(V) was located predominantly in the roots. The Cr(V) peak exhibited hyperfine splittings of about 0.79 gauss, typical of the Cr(V) complexes with diol-containing molecules. The results suggest that the reduction of Cr(VI) to lower oxidation states by living plants may provide a detoxification pathway for Cr(VI) in ecological systems. The results also indicate that low-frequency EPR may be used to investigate the metabolism of paramagnetic metal ions in intact plants.

Chlorophyta↗

In vivo oximetry using EPR and India ink.

Recent advances in electron paramagnetic resonance (EPR) oximetry have established the use of the particulate materials fusinite and lithium phthalocyanine (LiPc) as probes for measurement of oxygen tensions in tissues in vivo with a sensitivity and accuracy that is relevant for studying pathophysiological processes. India ink, another potentially very useful new probe for EPR oximetry, shares the critical properties of fusinite and LiPc and has the additional advantage of already having been widely used clinically with no apparent toxicity. The line width is particularly sensitive to changes in oxygen tension of less than 30 mmHg; in this range the line broadening/unit of pO2 is much greater than that of fusinite and LiPc. Over the range of biological conditions that can occur in vivo, the response of the EPR spectrum of India ink to pO2 is independent of pH, oxidants, reductants, and the nature of the medium. In this paper we describe the relevant properties of India ink and its use to measure pO2 in vivo in experimental animals and a human subject.

Adenocarcinoma↗

An analysis of the effects of eddy currents on L-band EPR spectra.

Recently, impressive results have been obtained with EPR studies of living animals and perfused organs using low-frequency EPR. In many instances in such studies, however, there are apparent distortions of the spectra. The shapes of these spectra and theoretical considerations indicate that these effects are due to eddy currents in the moderately conductive biological materials. Therefore the effects of eddy currents produced in biological samples under typical conditions being employed for in vivo EPR studies have been systematically studied in order to determine the extent of these effects and to develop methods for compensating for these effects. The presence of eddy currents was found to decrease the Q factor and distort the shapes of the EPR spectra. The distortion of the spectra led to linewidth broadening, changes in peak heights, and shifts of the apparent center of the lines. These effects could be corrected instrumentally, but this was effective only when signals have a high S/N. The use of appropriate computer simulations, based on linear combinations of the expected absorption and dispersion signals, can effectively correct for the effects of eddy currents and provide accurate data on the parameters of EPR spectra that are needed for most or all of the analyses used in biological studies of animals and tissues at low frequencies.

Animals↗

Magnetic brain stimulation: safety studies.

We describe short-term and long-term safety studies after low repetition rate magnetic brain stimulation in 10 normal subjects. We obtained quantitative EEG data, psychometric test results, serum prolactin and cortisol levels before and after brain stimulation. EEG and psychometric data were also obtained in 5 of these subjects 16-24 months after the initial experiment. Short- and long-term studies did not show any deleterious effects. Randt delayed recalls, however, showed a transient reduction in the score immediately after stimulation which resolved on retesting in 2 weeks. To address the question of fatigue we repeated Randt tests in 4 subjects before and after magnetic brain stimulation but without the other extensive psychometric, EEG and blood tests. Pre- and post-stimulation scores on this occasion showed no significant difference in these 4 subjects suggesting that the transient changes in the previous Randt score were related to fatigue. We conclude that single-pulse magnetic brain stimulation has no deleterious effects after magnetic brain stimulation.

Adult↗

India ink: a potential clinically applicable EPR oximetry probe.

Using a material that already is in widespread use in humans, India ink, the first EPR measurements in a human have been made, using the India ink in a pre-existing tattoo. The EPR spectra of India ink are very sensitive to the partial pressure of oxygen (pO2), thereby making it feasible to use this approach to measure pO2 in tissues in patients. This potentially provides a means to measure this parameter directly with a sensitivity, accuracy, and repeatability that have not been available previously, and thereby to be able to individualize and guide treatment of diseases such as cancer and peripheral vascular insufficiency.

Animals↗

Physical and instrumental considerations in the use of lithium phthalocyanine for measurements of the concentration of the oxygen.

The use of crystals of lithium phthalocyanine (LiPc) to measure the concentration of oxygen in vivo and in vitro by electron paramagnetic resonance leads to experimental constraints due to the very narrow EPR lines that may occur (as narrow as 11-13 mG in the absence of O2), distortions induced by the automatic frequency control system, anisotropy in the spectra (orientation-dependent linewidth is 11-17 mG in the absence of O2), microwave power saturation, and the effect of physiological motion. These constraints can be overcome if recognized. This article highlights the experimental and theoretical basis of these properties of the EPR signal of LiPc and suggests some technical solutions. It is most important to recognize that paramagnetic species such as LiPc present problems that are not commonly encountered in EPR spectroscopy.

Electron Spin Resonance Spectroscopy↗

Lithium phthalocyanine: a probe for electron paramagnetic resonance oximetry in viable biological systems.

Lithium phthalocyanine (LiPc) is a prototype of another generation of synthetic, metallic-organic, paramagnetic crystallites that appear very useful for in vitro and in vivo electron paramagnetic resonance oximetry. The peak-to-peak line width of the electron paramagnetic resonance spectrum of LiPc is a linear function of the partial pressure of oxygen (pO2); this linear relation is independent of the medium surrounding the LiPc. It has an extremely exchange-narrowed spectrum (peak-to-peak line width = 14 mG in the absence of O2). Physicochemically LiPc is very stable; its response to pO2 does not change with conditions and environments (e.g., pH, temperature, redox conditions) likely to occur in viable biological systems. These characteristics provide the sensitivity, accuracy, and range to measure physiologically and pathologically pertinent O2 tensions (0.1-50 mmHg; 1 mmHg = 133 Pa). The application of LiPc in biological systems is demonstrated in measurements of pO2 in vivo in the heart, brain, and kidney of rats.

Animals↗

Simultaneous multi-site EPR spectroscopy in vivo.

A gradient technique to measure electron paramagnetic resonance spectra simultaneously at several different locations is described. The technique is based on the use of point probes containing paramagnetic centers. The value of the magnetic field gradient is chosen to be sufficient to separate the EPR signals from the different paramagnetic probes yet at the same time small enough to change only minimally the shape of individual signals. The conditions to apply this technique are considered in detail. When experimental data have a high signal-to-noise ratio, the lineshape distortion induced by the gradient can be corrected with the aid of a known distribution function of paramagnetic centers within the probe. The maximum entropy deconvolution algorithm is successfully applied for the correction of significantly distorted lines. The technique is experimentally tested and applied to measure the concentration of oxygen in hypertrophied rat myocardium and normal rat kidney in vivo by low frequency EPR (L-band, 1.2 GHz). Two types of EPR oxygen-sensitive probes--lithium phthalocyanine crystals and synthetic carbohydrate chars--were used.

Animals↗