Coexistence of Neoplasia and Cortical Dysplasia in Patients Presenting with Seizures

Summary: Tumors and cortical dysplasia are associated with epilepsy, but few studies have examined the coexistence of neoplasia and dysplasia in these patients. We studied 13 patients (age 4–29 years) with recurrent seizures of 1 month to 21-year' duration (median 72 months). Ten patients were aged <21 years. Imaging studies localized the lesion to the temporal lobe (10 patients), parietal lobe (2 patients), and frontal lobe (1 patient). Tumors included ganglioglioma (8 patients), dysembryoplastic neuroepithelial tumor (DNT) (3 patients), and low-grade as- trocytoma (2 patients). Cortical dysplasia, including atypical aggregates of neurons (6 patients), multifocal loss of the cortical laminar architecture (7 patients), and neurons in the molecular layer of the cortex (3 patients) were observed near but separate from the tumor. Coexistence of certain tumors with cortical dysplasia, most frequently observed in the pediatric population, suggests a hamar-tomatous/dysplastic nature of the neoplasms.     

Human dolasetron pharmacokinetics: II Absorption and disposition following single-dose oral administration to normal male subjects

Dolasetron is a 5-hydroxytryptamine antagonist active at type III receptors; it is presently undergoing clinical evaluation for the reduction/prevention of cancer chemotherapyinduced nausea and vomiting. A previous study demonstrated that following intravenous administration to healthy male subjects, dolasetron disappeared extremely rapidly from plasma, and less than 1 per cent of the dose appeared in the urine. A major plasma metabolite, reduced dolasetron, peaked rapidly in the plasma. In this study, dolasetron was administered orally to healthy male subjects at doses ranging from 50 to 400 mg (mesylate monohydrate). Plasma concentrations of dolasetron were low and sporadic, and there was little excreted in urine; this prevented dolasetron pharmacokinetic analysis. Reduced metabolite concentrations peaked rapidly, with a median value of 1.00 h. The median terminal disposition half-life was 7.80 h. Median values for fraction of dose excreted in urine and renal clearance were 22.2 per cent and 2.56 ml min^?1 kg^?1. Whereas areas under the plasma concentration—time curves were proportional to dose, renal clearance increased with dose (p < 0.05). However, given dose proportionality to AUC, this is probably of little therapeutic consequence. Since reduced dolasetron has significant anti-emetic activity in the ferret model, it appears that this metabolite may play a significant role in pharmacodynamic activity.     

Seizure Elicitation Blocked by Pretreatment with Lidocaine

A patient is reported in whom pretreatment with intravenous lidocaine resulted in failure to elicit a seizure even at stimulus intensity markedly greater than that used successfully at prior and subsequent treatments. Together with one other report, this experience suggests that lidocaine may prevent a seizure by raising the seizure threshold. An alternative explanation is proposed for the classic findings of Ottosson that lidocaine-modified seizures are reduced in therapeutic efficacy.     

“Afterwork”: A clinical-phenomenological report

This paper explores a number of the dimensions of the process of afterwork: the psychological work that former patients engage in after treatment has terminated. Ten former patients, who had worked with 10 different therapists, were interviewed utilizing a semi-structured interview protocol, and their experiences form the basis for the findings and observations that are described. It was found that subjects remembered little by way of lessons or insights; rather, what remained with them were changes of perspective, the internalization of the process of the treatment, and the experience of their therapists' human qualities. In addition, it was found that most subjects had had some form of contact with their therapists post-termination. The implications of these findings are discussed.     

Arterial endothelial function in a porcine model of early stage atherosclerotic vascular disease

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States and is projected to become the leading cause of mortality in the world. Atherosclerosis is the most important single factor contributing to this disease burden. In this study, we characterize relationships between endothelial dysfunction and vascular disease in an animal model of diet-induced, early-stage atherosclerotic vascular disease. We tested the hypothesis that hypercholesterolaemia induces vascular disease and impairs endothelium-dependent relaxation (EDR) in conduit arteries of adult male Yucatan pigs. Pigs were fed a normal fat (NF) or high fat cholesterol (HFC) diet for 20-24 weeks. Results indicate that, while the HFC diet did not alter EDR in femoral or brachial arteries, EDR was significantly decreased in both carotid and coronary arteries. Sudanophilic fatty streaks were significantly present in the abdominal aorta and common carotid artery. Histopathology revealed increased intima-media thickness (IMT) and foam cell accumulation in Stary Stage I-III lesions in the abdominal aorta, common carotid artery and femoral arteries. In the coronary arteries, the accumulation of foam cells in Stary Stage I and II lesions resulted in a trend for increased IMT. There was no evidence of vascular disease in the brachial arteries. These results indicate that early stages of CVD (Stary Stage I-III) precede decreases in EDR induced by HFC diet, because femoral arteries exhibited foam cell accumulation and an increased IMT but no change in endothelial function.     

Local production of IgA- and IgM-rheumatoid factors in adult periodontal disease

The enzyme-linked immunospot assay was used to enumerate both the number and the frequency of spontaneous IgG, IgA, and IgM immunoglobulin-secreting cells and IgA- and IgM-rheumatoid factor (RF)-producing cells present in the gingivae and peripheral blood of adult periodontitis patients. Cells from 29 patients were incubated on plates coated with human IgG, Fc, or F(ab)₂ fragments and on plates coated with class-specific antihuman antibodies and secreted antibodies were subsequently visualized by means of an immunoenzymatic procedure. The data indicate that (1) IgA-RF- and IgM-RF-secreting cells are frequently present in the gingiva of adult periodontitis patients; (2) production of RF in gingivae of adult periodontitis patients occurs in the absence of demonstrable RF production by simultaneously obtained peripheral blood mononuclear cells, suggesting that local autoimmune reactions may occur in this disease; and (3) lack of correlation between IgA-RF and IgM-RF production in diseased gingiva suggests that the two RF isotypes are regulated independently of each other.     

High-resolution analysis of locomotor activity rhythms indisconnected,a visual-system mutant ofDrosophila melanogaster

Free-running locomotor activity and eclosion rhythms ofDrosophila melanogaster, mutant at thedisconnected (disco) locus, are substantially different from the wild-type phenotype. Initial periodogram analysis revealed little or no rhythmicity (Dushayet al., 1989). We have reanalyzed the locomotor activity data using high-resolution signal analysis (maximum-entropy spectral analysis, or MESA). These analyses, corroborated by autocorrelograms, uncovered significant residual circadian rhythmicity and strong ultradian rhythms in most of the animals tested. In this regard thedisco mutants are much like flies expressing mutant alleles of theperiod gene, as well as wild-type flies reared throughout life in constant darkness. We hypothesize that light normally triggers the coupling of multiple ultradian oscillators into a functional circadian clock and that this process is disrupted indisco flies as a result of the neural lesion.This work was supported in part by NIH Grant FM-33205.