Analysis of the EEG dynamics of epileptic activity in gelastic seizures using decomposition in independent components.

OBJECTIVE: Gelastic seizures are a frequent and well established manifestation of the epilepsy associated with hypothalamic hamartomas. The scalp EEG recordings very seldom demonstrate clear spike activity and the information about the ictal epilepsy dynamics is limited. In this work, we try to isolate epileptic rhythms in gelastic seizures and study their generators. METHODS: We extracted rhythmic activity from EEG scalp recordings of gelastic seizures using decomposition in independent components (ICA) in three patients, two with hypothalamic hamartomas and one with no hypothalamic lesion. Time analysis of these rhythms and inverse source analysis was done to recover their foci of origin and temporal dynamics. RESULTS: In the two patients with hypothalamic hamartomas consistent ictal delta (2-3 Hz) rhythms were present, with subcortical generators in both and a superficial one in a single patient. The latter pattern was observed in the patient with no hypothalamic hamartoma visible in MRI. The deep generators activated earlier than the superficial ones, suggesting a consistent sub-cortical origin of the rhythmical activity. CONCLUSIONS: Our data is compatible with early and brief epileptic generators in deep sub-cortical regions and more superficial ones activating later. SIGNIFICANCE: Gelastic seizures express rhythms on scalp EEG compatible with epileptic activity originating in sub-cortical generators and secondarily involving cortical ones.     

Linguistic Validation of the US Spanish Work Productivity and Activity Impairment Questionnaire, General Health Version

INTRODUCTION: There are no measures of health-related absenteeism and presenteeism validated for use in the large and increasing US Spanish-speaking population. Before using a Spanish translation of an available English-language questionnaire, the linguistic validity of the Spanish version must be established to ensure its conceptual equivalence to the original and its cultural appropriateness. OBJECTIVE: The objective of this study was to evaluate the linguistic validity of the US Spanish version of the Work Productivity and Activity Impairment questionnaire, General Health Version (WPAI:GH). METHODS: A US Spanish translation of the US English WPAI:GH was created through a reiterative process of creating harmonized forward and back translations by independent translators. Spanish-speaking and English-speaking subjects residing in the US self-administered the WPAI:GH in their primary language and were subsequently debriefed by a bilingual (Spanish-English) interviewer. RESULTS: US Spanish subjects (N = 31) and English subjects (N = 35), stratified equally by educational level, with and without a high school degree participated in the study. The WPAI-GH item comprehension rate was 98.6% for Spanish and 99.6% for English. Response revision rates during debriefing were 1.6% for Spanish and 0.5% for English. Responses to hypothetical scenarios indicated that both language versions adequately differentiate sick time taken for health and non-health reasons and between absenteeism and presenteeism. CONCLUSION: Linguistic validity of the US Spanish translation of the WPAI:GH was established among a diverse US Spanish-speaking population, including those with minimal education.     

The contribution of reoxygenation to ischemic brain damage

This study examined the hypothesis that the level of postischemic reperfusion affects the severity of the resulting neuronal necrosis. In rats, tissue PO2% was monitored as an index of flow (reoxygenation) at four cortical sites by chronically implanted platinum electrodes. Twenty minutes of total global cerebral ischemia was followed by 30 min of reoxygenation. The level of reoxygenation was controlled to maintain the PO2 nearly constant at one or more of the cortical electrodes. Tissue from within 400 microns of each of 19 electrode sites among seven rats was evaluated histologically. There was a positive correlation between reoxygenation level and severity of neuronal damage. Perineuronal lucent halo formation, probably representing astrocyte foot process swelling, was negatively correlated with reoxygenation level. This study demonstrates that ischemic neuronal damage was aggravated by increased reoxygenation but that perineuronal swelling, as evidenced by halo formation, was somewhat ameliorated.     

Atrial natriuretic factor--its possible role in the pathogenesis and therapy of arterial hypertension

Using radioimmunoassay the authors investigated the plasma concentration of the immunoreactive atrial natriuretic factor (IR-ANF) and its content in the atria of 4-, 8-, 12-, 16-, and 20-weeks-old spontaneously hypertensive rats (SHR), and compared the results with data obtained in normotensive Wistar-Kyoto rats of the same age. With hypertension accelerating in SHR between the 8th and the 20th weeks of life, IR-ANF content in the atrium gradually decreased, and the plasma IR-ANF concentration increased. The decline in IR-ANF was due to its decrease primarily in the left atrium. Long-term (6-day) administration of synthetic ANF to SHR with fully developed hypertension led to normalization of BP. The results do not support the hypothesis that arterial hypertension in SHR is induced by a primary deficiency of ANF. The changes in IR-ANF in the atria and plasma occur rather as an adaptive and regulatory response to increasing BP. Prolonged administration of ANF to SHR had a hypotensive effect. Therapeutic application of ANF in man depends on the development of oral and long-acting analogues.     

Quantitative analysis of contrasuppressor T lymphocytes in leprosy; induction of Ia antigens with gamma interferon

Lepromatous leprosy is characterized by immune anergy and abnormal suppressor T-cell function. Contrasuppressor cells are a subset of CD8+, vicia villosa-adherent T lymphocytes. T-contrasuppressor (Tcs) cells act on T-helper cells to cause them to become unresponsive to the action of T-suppressor cells. In 8 lepromatous (LL) and 7 tuberculoid (TT) patients, and 6 healthy contacts we studied the percent of the following lymphocyte subsets: CD3+, CD4+, CD8+, Ia+, vicia villosa+ (VV+), CD8, VV+, VV, Ia+, and Ia, Tac+. This was done in baseline status as well as post-stimulation with recombinant gamma interferon (rIFN-gamma). We found that peripheral blood mononuclear cells from LL and TT patients and controls exhibit a similar number of putative contrasuppressor lymphocytes (CD8, VV+ cells). However, in the contrasuppressor subset from LL patients we found a low percent of Ia+ (p less than 0.05 compared to controls or TT). In the three groups studied, the rIFN-gamma enhanced the percent of Ia+ lymphocytes in the CD8, VV+ cell subpopulation. However, the CD8, VV+ lymphocytes from LL patients, despite the effect of rIFN-gamma, continue to have a low percent of Ia+ cells (p less than 0.05 compared to controls or TT). These findings suggest that LL patients might have abnormalities in the contrasuppressor immune circuit. Future functional studies on the role of Tcs cells in the anergy seen in LL will be required in order to define the apparent dysfunction occurring in this disease.     

Differential Effects of Anesthetics on Mitochondrial KATP Channel Activity and Cardiomyocyte Protection

Background: Mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels play a pivotal role in mediating cardiac preconditioning. The effects of intravenous anesthetics on this protective channel have not been investigated so far, but would be of importance with respect to experimental as well as clinical medicine.

Methods: Live cell microscopy was used to visualize and measure autofluorescence of flavoproteins, a direct reporter of mitoKATP channel activity, in response to the direct and highly selective mitoKATP channel opener diazoxide, or to diazoxide following exposure to various anesthetics commonly used in experimental and clinical medicine. A cellular model of ischemia with subsequent hypoosmolar trypan blue staining served to substantiate the effects of the anesthetics on mitoKATP channels with respect to myocyte viability.

Results: Diazoxide-induced mitoKATP channel opening was significantly inhibited by the anesthetics R-ketamine, and the barbiturates thiopental and pentobarbital. Conversely, urethane, 2,2,2-trichloroethanol (main metabolite of [alpha]-chloralose and chloral hydrate), and the opioid fentanyl potentiated the channel-opening effect of diazoxide, which was abrogated by coadministration of chelerythrine, a specific protein kinase C inhibitor. S-ketamine, propofol, xylazine, midazolam, and etomidate did not affect mitoKATP channel activity. The significance of these modulatory effects of the anesthetics on mitoKATP channel activity was substantiated in a cellular model of simulated ischemia, where diazoxide-induced cell protection was mitigated by R-ketamine and the barbiturates, while urethane, 2,2,2-trichloroethanol, and fentanyl potentiated myocyte protection.