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Biomedical subjects

J Engel

Publications and source records attributed to J Engel.

791 records · Page 44Linked to original sources
PubMedDate not supplied

Vasoactive intestinal peptide in cerebrospinal fluid.

Immunoreactive vasoactive intestinal peptide (VIP) was measured in lumbar and ventricular cerebrospinal fluid (CSF) from patients with various neurological disorders and in 2 hour aliquots of cisternal fluid removed continuously from rhesus monkeys. Although most of the VIP in concentrated pools of human ventricular fluid and of monkey cisternal fluid co-eluted with synthetic porcine VIP28 on a column of Sephadex G-25 superfine, there was evidence that smaller immunoreactive fragments were also present. A circadian pattern of CSF VIP concentration was observed in 2 of the 3 monkeys studied, with highest levels occurring at night and lowest during the day. Ventricular fluid VIP levels were highest in hydrocephalic children and lowest in patients with multiple sclerosis or epilepsy, while VIP was not detectable in ventricular fluid from patients in coma following a severe head injury. There were no significant differences in VIP concentrations in CSF from patients with dystonia. Parkinson's disease, or Alzheimer's disease, suggesting that VIP containing neurons are not affected in these disorders. Lumbar fluid VIP levels were low in patients undergoing aneurysm surgery. Since VIP is a potent vasodilator, these findings may have important implications in relation to the development of vasospasm following subarachnoid hemorrhage.

Chromatography, Gel↗
PubMedDate not supplied

Effects of the 5-HT receptor agonist, 8-OH-DPAT, on ethanol preference in the rat.

Clinical and animal studies have suggested that consumption of ethanol is influenced by the central serotonergic (5-HT) transmission system. In the present study this hypothesis was tested by observing the effects of a selective 5-HT receptor agonist, 8-OH-DPAT, on ethanol preference in the rat. The rats had access to a 6% (v/v) ethanol solution and water during baseline and treatment periods. Based on the baseline recordings, 2 groups of rats were formed: A high preference group (ethanol intake greater than 50% of total fluid intake) and a low preference group (ethanol intake less than 30%). Both groups were treated SC with 0.125 mg/kg 8-OH-DPAT twice daily for 3 days. The treatment caused a significant reduction of ethanol consumption in the high preference group, but no change in the low preference group. The findings support the hypothesis that activation of the 5-HT system reduces ethanol intake. This effect was restricted to the high preferring rats, suggesting that 8-OH-DPAT interferes only with the positive reinforcing effect of ethanol.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMedDate not supplied

Effects of chronic naloxone pretreatment on amygdaloid kindling in rats.

Effects of chronic naloxone pretreatment (75 or 270 micrograms/h for 14 days) on the development of amygdaloid kindling in rats were evaluated. The acquisition of seizure activity was modified in the naloxone pretreated animals, depending on the nucleus stimulated: facilitation of stages IV and V occurred in 37%, variability of electrographic and behavioral responses to electrical stimulation during the kindling development in 33%, and facilitation of stages IV and V followed by long periods of seizure suppression in 29%. Enhancement of postictal seizure suppression during a recycling paradigm was observed in all the naloxone pretreated rats. It was concluded that the chronic administration of naloxone (known to induce opioid binding upregulation and supersensitivity), in association with the enduring changes in opioid mechanisms provoked by kindled seizures, were responsible for the facilitation and suppression of epileptic activity. These findings support bidirectional modulatory effects of opioid peptides on epileptic seizures as well as the view that epileptic seizures can induce enduring alterations in opioid mechanisms.

Amygdala↗
PubMedDate not supplied

Interictal cerebral metabolism in partial epilepsies of neocortical origin.

We performed interictal [18F]fluorodeoxyglucose positron emission tomography (FDG PET) in 24 patients with partial epilepsy of neocortical origin. Two-thirds of patients had regions of hypometabolism. The zone of intracranially recorded electrographic ictal onset was always located in a region of hypometabolism, in those with hypometabolism. Hypometabolic regions in partial epilepsies of neocortical origin were usually associated with structural imaging abnormalities. Regional hypometabolism occasionally occurred without localizing ictal scalp EEG and cerebral magnetic resonance imaging findings, however. FDG PET may be useful in directing placement of intracranial electrodes for presurgical evaluation of refractory neocortical seizures.

Adolescent↗
PubMedDate not supplied

The LHRH antagonist cetrorelix: a review.

In those clinical situations in which an immediate and profound suppression of gonadotrophins is desired, LHRH agonists have the disadvantage of producing an initial stimulatory effect on hormone secretion. Therefore, the use of GnRH antagonists which cause an immediate and dose-related inhibition of LH and FSH by competitive blockade of the receptors is much more advantageous. One of the most advanced antagonist produced to date is Cetrorelix, a decapeptide which has been shown to be safe and effective in inhibiting LH and sex-steroid secretion in a variety of animal species and in clinical studies as well. Clinical trials in patients suffering from advanced carcinoma of the prostate, benign prostate hyperplasia, and ovarian cancer are currently in progress and have already shown the usefulness of this new treatment modality. In particular, the concept that a complete suppression of sex-steroids may not be necessary in indications such as uterine fibroma, endometriosis and benign prostatic hyperplasia represents a promising novel perspective for treatment of these diseases. Following completion of phase III trials in controlled ovarian stimulation for IVF regimens, Cetrorelix was given marketing approval and, thus, became the first LHRH antagonist available clinically.

Animals↗
PubMedDate not supplied

Mesial temporal spikes: a simultaneous comparison of sphenoidal, nasopharyngeal, and ear electrodes.

A prospective study was performed to compare the relative ability of sphenoidal (SP), nasopharyngeal (NP), and ear electrodes for detecting mesial temporal lobe epileptiform discharges. Forty-four EEGs were performed on patients with complex partial seizures, simultaneously recording from NP, SP, and ear electrodes. Spikes were noted in SP derivations in 25 records, in ear derivations in 23 records, and in NP derivations in 20 records. A total of 875 spikes were counted, SP showing 99%, NP 57%, and ear 54% of discharges, with greatest amplitudes generally seen in SP derivations. The Mann-Whitney rank sum test showed SP electrodes superior to both NP and ear electrodes (p less than 0.0001) and no significant differences between NP and ear electrodes. We conclude that SP electrodes are superior to both NP and ear electrodes in detecting mesial temporal spikes.

Brain↗
PubMedDate not supplied

Interhemispheric propagation time of human hippocampal seizures. I. Relationship to surgical outcome.

This study evaluated ictal stereotaxic electroencephalogram (SEEG) records in 75 patients with complex partial seizures who later received anterior temporal lobectomy and were evaluated for long-term seizure relief. The time required for seizures to propagate from the putatively epileptogenic hippocampal formation to the contralateral hippocampal formation was measured from 615 ictal SEEG records. These interhemispheric propagation times were then compared with the degree of post-lobectomy seizure relief. Poor postsurgical seizure relief was associated with seizure propagation times of less than or equal to 5 s. Relief or reduction of seizures after surgery was associated with seizure propagation times greater than 50 s. These relationships were also found to occur in a subset of 56 patients who did not exhibit interhemispheric propagation times of less than 0.5 s, thus indicating that interhemispheric propagation times in the range of 0.5-5 s is a negative prognostic sign even in the absence of "bilaterally synchronous" ictal SEEG onsets. The finding of longer interhemispheric propagation times in patients who were improved by surgery may be accounted for by the greatly reduced size, or absence, of the hippocampal commissure in humans and suggests that the corpus callosum is a major, albeit indirect, route by which hippocampal foci may propagate seizure activity contralaterally. The finding of shorter interhemispheric propagation times in patients who did poorly after surgery may be accounted for by the existence of foci outside the region of excision with more direct access to callosal pathways or, alternatively, by the presence of damage in a more seizure-prone contralateral hippocampus.

Electroencephalography↗
PubMedDate not supplied

Prognostic significance of independent auras in temporal lobe seizures.

We performed a retrospective study of auras that occurred independently of complex partial seizures in patients undergoing continuous EEG monitoring with stereotactically implanted depth electrodes placed in mesiotemporal structures. Forty of 54 patients had a history of independent auras, and 32 of these individuals had independent auras while being monitored. Two hundred ninety-two independent auras were recorded, and EEG characteristics and subjective symptoms were analyzed with regard to surgical outcome. Most patients had ictal EEG changes with all or some of their auras. Four patients had nonlocalized or multifocal complex partial seizures despite the presence of well-localized auras, indicating that if intracranial ictal recording is used as a gold standard for localization, complex partial seizures must be recorded. Presence or absence of EEG change with auras did not affect prognosis nor did variability of ictal EEG pattern, spatial extent of initial field potential, aura duration, or character of symptoms correlate with prognosis or postoperative persistence of auras.

Electroencephalography↗
PubMedDate not supplied

Quantitative comparison of cell loss and thiopental-induced EEG changes in human epileptic hippocampus.

Thiopental-induced EEG beta activity recorded from mesial and lateral temporal lobe sites was analyzed both visually and by computer in 30 patients with complex partial seizures. All patients later received anterior temporal lobectomy. Volumetric cell densities and percentage of principal cell loss relative to normal controls were determined in several different areas of each resected temporal lobe. The percentage of drug-induced beta activity was then compared with the percentage of cell loss by (a) making precise topographic correlations between induced beta and cell loss, (b) relating the overall degree of left/right beta asymmetry to cell loss averaged over wide regions, and (c) comparing the likelihood of left/right beta asymmetries in patients with and without extreme cell loss. The results obtained were consistently negative and were unaffected by whether EEG data were analyzed by computer or visual inspection. These results indicate that the well-known loss of drug-induced beta activity found in epileptogenic regions is not an indicator of the degree of cell loss or sclerosis. The underlying focal dysfunction measured by EEG beta activity remains unknown, and factors such as focal hypoperfusion, hypometabolism, and the microanatomic features of the cells remaining in the focus should be investigated.

Beta Rhythm↗
PubMedDate not supplied

Role of the frontal lobes in the propagation of mesial temporal lobe seizures.

The depth ictal electroencephalographic (EEG) propagation sequence accompanying 78 complex partial seizures of mesial temporal origin was reviewed in 24 patients (15 from the University of Pittsburgh Epilepsy Center and 9 from UCLA). All patients were monitored with bilateral mesial frontal and mesial temporal depth electrodes and later received anterior temporal lobectomy. Ictal EEG records were categorized according to sequence of spread from the temporal focus to the other regions. Although propagation patterns varied both within and between patients, certain features were notable: (a) It was very common for seizure activity to spread initially to the ipsilateral frontal lobe (observed in 22 of 24 patients). (b) The most common mode of spread (15 of 24 patients) was initiating temporal lobe----ipsilateral frontal lobe----contralateral frontal lobe----contralateral temporal lobe. (c) Occasionally, seizure discharges invaded the frontal lobes but failed to invade the contralateral temporal lobe (2 of 24 patients). (d) Seizure activity occasionally invaded the contralateral temporal lobe prior to invading the frontal lobes (2 of 24 patients). Other notable features included (i) a clear tendency for mesial temporal seizure discharges initially to invade orbitofrontal (as opposed to anterior cingulate) cortex and (ii) the emergence of a period of clear asymmetry in the frontal lobes during which high-amplitude, rapid discharges were present on the side ipsilateral to the initiating temporal lobe. These results suggest that the prefrontal region, especially the orbitofrontal cortex, is strongly influenced by mesial temporal ictal activity. This region appears to be frequently involved in the propagation of seizures initiated in the mesial temporal lobe and may play a role in the interhemispheric propagation of mesial temporal seizures.

Brain Mapping↗
PubMedDate not supplied

Quality of life of epilepsy surgery patients as compared with outpatients with hypertension, diabetes, heart disease, and/or depressive symptoms.

Health-related quality of life (HRQOL) of 166 adults who had previously undergone surgical treatment for intractable epilepsy was compared with that of outpatients with hypertension, diabetes, heart disease, and/or depressive symptoms. Eight self-reported HRQOL domains were evaluated and compared by the RAND 36-Item Health Survey 1.0: emotional well-being, social function, role limitations due to emotional problems, energy/fatigue, pain, role limitations due to physical problems, physical function, and general health perceptions. A pictorial item on overall QOL was also administered, for a total of 9 HRQOL domains. With adjustment made for age, gender, education, and comorbid conditions, 55 completely seizure-free patients scored higher (i.e., better health) than patients with hypertension in 6 of 9 domains, higher than diabetic patients in 8 of 9, higher than those with heart disease in all 9, and higher than those with depressive symptoms in all 9 (all p < 0.05). Sixty-seven patients still having seizures with impaired consciousness scored worse than hypertensive patients in 5 domains, worse than diabetic patients in 3, and worse than heart disease patients in 2; for all 3 conditions, these domains included emotional well-being and overall QOL (p < 0.05). These 67 patients, however, scored better than patients with depressive symptoms in all 9 domains, better than those with heart disease in 2, and better than those with diabetes in 1 (all p < 0.05). Forty-four other patients had only simple partial seizures (SPS); their scores were comparable to those of diabetic and heart disease patients on mental and social health scales but were higher ("better") than those of these patients on physical health scales. HRQOL among patients who have undergone "curative" epilepsy surgery is better than that of patients who have hypertension, diabetes, heart disease, or depressive symptoms. Patients who have continued seizures with altered consciousness are worse off in terms of emotional well-being and overall QOL than all other patients, except for those with depressive symptoms.

Ambulatory Care↗
PubMedDate not supplied

Changes of intracellular calcium, fatty acids and phospholipids during miltefosine-induced apoptosis monitored by fluorescence- and 13C NMR-spectroscopy.

The alkylphosphocholine Miltefosine (hexadecylphosphocholine, HePC) induces apoptosis in human epithelial KB cells, whereas no such effect can be observed in a resistant clone (KBres). Its mode of action is mediated via the cell membrane, whereas the mechanism is still widely unknown. The use of various spectroscopic methods (fluorescence spectroscopy with Fura-2/AM on viable cells, 13C NMR spectroscopy on lipid extracts) reveals osmotic and metabolic changes in HePC treated sensitive cells. Intracellular free Ca(2+)-concentration increased over 300% of control in apoptotic cells, whereas KBres cells showed only a minor increase and no morphological response typical for apoptosis. The Ca(2+)-influx was mediated via calcium channels in the cell membrane. The HePC-induced influx is prevented by Gd3+, which blocks those calcium channels. Cells, grown in Ca(2+)-free medium, showed no apoptotic behaviour after treatment with HePC. If apoptosis was induced, an increased fatty acid and subsequent phospholipid biosynthesis was observed. This effect seems to be a specific marker of apoptosis in KB cells.

Antineoplastic Agents↗
PubMedDate not supplied

Early stage monitoring of miltefosine induced apoptosis in KB cells by multinuclear NMR spectroscopy.

Synthetic ether lipids, like miltefosine (hexadecylphosphocholine), an alkylphosphocholine, are antineoplastic agents in vitro and in vivo. Their mode of action is mediated via the cell membrane, but the mechanism is still unclear. Miltefosine induces apoptosis in human epithelial KB cells, but slows down only proliferation in rat C6 glioma cells. NMR spectroscopy on lipid extracts reveals increased diacylglycerol and triacyglycerol biosynthesis in KB cells prior to DNA fragmentation indicating a CTP:phosphocholine-cytidylyl-transferase (CT) inhibition by the drug. Although C6 cells were morphologically affected by alterations in phospholipid composition and metabolism by a long term treatment (23 days) with the drug, no persistent diacylglycerol increase is observed.

Animals↗