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Biomedical subjects

E Novotny

Publications and source records attributed to E Novotny.

16 recordsLinked to original sources

[Duration of induced seizures during selective pharyngeal brain cooling].

Whole body hypothermia can be used to treat the injured brain (e.g. after hypoxic events). Side effects include hemodynamic instability, coagulopathy and infection. Because of these side effects it appears reasonable to cool the brain selectively (selective brain cooling, SBC) without changing the core temperature. A new animal model was used to demonstrate SBC from the pharynx and to examine effects of SBC on the duration of pharmacologically induced seizure activity. Sprague-Dawley rats (n=18, 12 successful experiments) were sedated and mechanically ventilated. Invasive blood pressure monitoring was instituted and blood gases were drawn to evaluate the arterial blood gas status. Electrical brain activity was recorded using a microneedle in the extracellular compartment of the rat brain cortex. Cooled water was circulated through a small tubing into and out of the pharynx of the animals. The cortical as well as the rectal temperature were recorded. After the injection of a single dose of bicuculline (1 mg/kg i.v.) per animal the duration of the induced seizure activity was measured and compared with the temperature prior to the induction of seizure activity. The cortical blood flow (CBF) was detected using intra tissue Doppler signals in the rat cortex in the same location as the EP-study. The influence of a brain temperature reduction between 36.5 degrees to 31.5 degrees C on the seizure duration was examined. There was a positive correlation between the seizure duration and the cortical temperature (r=0.64). Also the CBF was increased during seizure activity (p=0.02) and the increase correlated weakly with cortical temperature (r=0.18). The core temperature remained in the normothermic range (36.9+/-0.7 degrees C) Conclusion: The duration of induced seizures correlates with local brain temperature. In the future further studies should examine the efficiency of induced (selective) brain cooling to treat prolonged seizure activity.

Animals↗

[Selective pharyngeal brain cooling].

Whole-body cooling can be used in the treatment of various brain pathologies, for example, after hypoxic events. Potential complications include haemodynamic instability, coagulation disorders and infection. Selective brain cooling (SBC) would therefore appear to make good sense. In an animal model a new approach to SBC was therefore evaluated. A rat weighing 350 g was sedated with alpha-chloralose (40 mg/kg/h) and d-tubocurarine (4.05 mg/kg/h), mechanically ventilated and placed on a heating pad. A thermocouple was introduced into the somatosensory cortex to a depth of 2.5 mm. SBC was achieved using a novel approach: PTFE tubing (ID 100 microns) with an inlet and an outlet was wrapped around and glued to a piece of wood, and introduced non traumatically into the pharynx. The tubing was perfused with cold water (+4 degrees C). Under SBC the cortical temperature dropped from 38.4 degrees C to 27.7 degrees C while the core temperature remained stable. In an animal model SBC was successfully accomplished via the pharynx. Further studies should now be done to evaluate the effectiveness of this approach in larger animals with potentially different anatomical features.

Animals↗

Estimating tissue deformation between functional images induced by intracranial electrode implantation using anatomical MRI.

This paper examines a solution to the general problem of accurately relating points within functional data acquired before and after subdural intracranial electrode implantation. We develop an approach based on nonrigid registration of high resolution anatomical MRI acquired together with the functional data. This makes use of a free-form B-Spline deformation model and registration is recovered by maximizing the normalized mutual information between the preimplant MRI and the postimplant MRI. We apply the approach to estimate the tissue deformation induced by the presence of intracranial electrodes over 15 patient studies. Maximum tissue displacements of 4 mm or greater were observed in all cases either in the cortex or around the ventricles due to CSF loss. In studies involving larger 4 x 4 grids, local tissue displacement estimates exceeded 10 mm from the preimplant brain shape. The key issue with this approach is whether the deformation estimates are contaminated by the presence of susceptibility-induced imaging artifacts. We therefore evaluate the deformation estimates in recovering alignment of essentially identical SPECT studies of eight patients acquired before and after electrode placement. An ROI-based analysis of the variance of resulting subtraction values between pre- and postimplant SPECT was carried out in regions of tissue below electrode grids. Results indicate for all cases a substantial reduction in residual SPECT subtraction artifacts to a level comparable to that in an equivalent region of undeformed tissue.

Adolescent↗

Proton magnetic resonance spectroscopy: clinical applications in children with nervous system diseases.

With the use of software modifications of existing magnetic resonance imaging technology, proton magnetic resonance spectroscopy yields insight noninvasively regarding brain biochemistry. Biochemical information can be obtained directly both regionally and longitudinally. This article summarizes the technological basis for magnetic resonance spectroscopy as well as its established applications to disorders of interest to the pediatric neurologist. Future directions for magnetic resonance spectroscopy study and advances to be expected in the near future are also highlighted.

Adolescent↗

Proton magnetic resonance spectroscopy: an emerging technology in pediatric neurology research.

Proton magnetic resonance spectroscopy (MRS) is an emerging technology that allows for the quantitative noninvasive assessment of regional brain biochemistry. The capacity to carry out MRS studies requires existing magnetic resonance imaging (MRI) technology platforms and the purchase of commercially available software modifications. In this review, the physical basis for MRS will be presented leading to an understanding of its potential applications and limitations within the clinical research milieu. Thus far, within pediatric neurology, proton MRS studies have been used to assist in the prediction of outcome in a variety of settings of acquired brain injuries (perinatal asphyxia, near drowning). In addition, proton MRS has been used to document disturbances in oxidative metabolism in neurometabolic disorders, assisting in defining phenotype and the response to therapeutic interventions. In epilepsy, spectroscopic studies have been useful in localizing the epileptogenic zone in intractable focal epilepsies. Future applications of proton MRS will also be highlighted. These include its use as a means of observing the transport and metabolism of various compounds in the brain, its concurrent application with other nuclear magnetic resonance techniques such as MRI and functional MRI, and finally its potential as a means of assessing the short-term effects of any CNS targeted pharmacologic interventions.

Brain↗

Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation.

Brain lactate concentration is usually assumed to be stable except when pathologic conditions cause a mismatch between glycolysis and respiration. Using newly developed 1H NMR spectroscopic techniques that allow measurement of lactate in vivo, we detected lactate elevations of 0.3-0.9 mM in human visual cortex during physiologic photic stimulation. The maximum rise appeared in the first few minutes; thereafter lactate concentration declined while stimulation continued. The results are consistent with a transient excess of glycolysis over respiration in the visual cortex, occurring as a normal response to stimulation in the physiologic range.

Energy Metabolism↗

Transient analysis for antiproliferative gene activity.

A subset of tumor suppressor genes presumably functions by the inhibition of cellular proliferation; however, antiproliferative activity after transfection with putative suppressor genes has been difficult to demonstrate and often requires lengthy selection either in nude mice or in vitro. A rapid alternative is presented here that utilizes a gene encoding a surface marker protein to identify transfectants in a transient expression assay. In this assay the labeling index, rate of DNA synthesis, cell-cycle distribution, and surface receptor display are measured by flow cytometry. Human beta-interferon, a gene with proven antiproliferative activity, was studied using the transient analysis system. The beta-interferon gene was introduced into human tumor cells along with the marker gene encoding the 55-kDa subunit of the human interleukin 2 receptor. Within a few days of transfection, analysis of transfectants by flow cytometry revealed a decrease in the fraction of cells in G2/M and an increase in the fraction of cells in G1/G0 and S phases. The distortion of the cell cycle was accompanied by as much as a 69% reduction in the rate of DNA synthesis and, in some experiments, an unanticipated increase in the labeling index. Therefore, cells accumulating in S phase were not blocked but continued to synthesize DNA although at a reduced rate. These studies on DNA synthetic rates revealed the caveat that screening for antiproliferative candidate genes with a labeling index alone could, in certain circumstances, exclude potentially interesting sequences from further consideration. Although this transient analysis system was developed for studies on cellular proliferation, it may prove suitable for phenotypic assays on other genes as well.

Bromodeoxyuridine↗

In vivo 31P and in vitro 1H nuclear magnetic resonance study of hypoglycemia during neonatal seizure.

To examine the hypothesis that hypoglycemia has an adverse effect on brain energy state during seizure, neonatal dogs were subjected to bicuculline-induced seizure while hyperglycemic, normoglycemic, or hypoglycemic. Cerebral blood flow increased and remained elevated in all animals subjected to seizure, regardless of blood or brain glucose concentration. In vivo 31P nuclear magnetic resonance spectroscopy disclosed a small (10-20%) decrease in adenosine triphosphate levels and a greater (20-40%) decline in phosphocreatine levels in animals experiencing seizure, irrespective of whether they were hyper-, normo-, or hypoglycemic. In vitro analysis of brain extracts with 1H nuclear magnetic resonance spectroscopy disclosed a significant elevation of lactate in all seizing animals. There were differences in brain alanine, glycine, and beta-hydroxybutyrate levels between the hyperglycemia-seizure and hypoglycemia-seizure groups. Alternate substrates such as lactate, fatty acids, or amino acids may be used when neonatal seizure is complicated by hypoglycemia, thereby preventing further deterioration of brain metabolic state.

Animals↗

Triple staining of normal and degenerating nervous tissue.

A method of counterstaining sections impregnated according to a previously reported modification of the Glees silver impregnation is described. The basis for this counterstain is the Klüver-Barrera luxol fast blue technique. The results are illustrated and the advantages and disadvantages of the procedure are discussed.

Animals↗

Ictal EEG changes with corpus callosum section.

Corpus callosum section diminishes but does not completely abolish secondary bilaterally synchronous interictal EEG discharges, yet often causes cessation of generalized seizures. The effects of corpus callosum section on ictal EEG patterns have not been described. We contrasted ictal EEG patterns before and after anterior callosotomy in 18 patients and before and after total callosotomy in 10 patients. Bilaterally synchronous seizure onset was disrupted in 5 of 11 anterior section patients and 5 of 5 total section patients. Seven of 18 anterior section patients and 5 of 10 total section patients had more localized seizure onset after the procedure; localization to the frontal lobe was observed after anterior or total section, but only total section patients had newly demonstrated posterior locations of seizure onset. These data suggest that the mechanisms by which bilaterally synchronous interictal and ictal discharges are generated differ. Although brainstem or diencephalic structures may contribute to formation of interictal bilateral synchrony, the corpus callosum may be the only pathway used in producing apparent bilateral synchronous seizure onset in patients with secondarily generalized seizures.

Brain Stem↗

Psychosocial aspects of oncology: challenges and problems of research in a radiotherapy center of a community hospital.

This paper describes the vicissitudes of psychosocial research in a radiotherapy center. The project described evaluates the efficacy of counseling techniques in patients with early stage breast cancer receiving radiotherapy. The problems involved are discussed. They include the effects of: 1) introducing a psychosocial program into a medical setting; 2) research, specifically psychological, on staff and treatment in a nonresearch center; 3) asking patients to participate in a project the relevance of which is not immediately apparent; and 4) working under such conditions on the research itself. Conclusions and recommendations derived from this experience are made.

Adaptation, Psychological↗

MR and CT in cytoplasmically inherited striatal degeneration.

A rare, cytoplasmically inherited striatal degeneration associated with Leber's optic atrophy exhibited selective symmetric low-density lesions in the putamen on the CT scan in five patients. The CT findings, however, were asymmetric (one patient) and subtle in the early phases of the disease. Occasionally, caudate lesions were demonstrable. On MR imaging, the lesions had high signal intensity on T2-weighted images and low signal intensity on T1-weighted images. This group of patients was distinguished from patients with other causes of striatal degeneration by a lack of hemispheric, brainstem, or cerebellar atrophy.

Adolescent↗