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J Engel

Publications and source records attributed to J Engel.

At least 289 records · Page 16Linked to original sources

Interictal metabolic anatomy of mesial temporal lobe epilepsy.

OBJECTIVE--To examine patterns of temporal and extratemporal regional interictal glucose hypometabolism in individual patients with unilateral mesial temporal lobe epilepsy (TLE). Previous reports disagree on which extratemporal areas can be hypometabolic in TLE. DESIGN--Case series of patients with TLE who underwent interictal fludeoxyglucose F 18 positron emission tomography, compared quantitatively with normal positron emission tomography. SETTING--Patients referred for surgical treatment of medically refractory complex partial seizures. PATIENTS AND OTHER PARTICIPANTS--Ten normal volunteers; 27 patients with TLE selected to exclude seizures of bilateral temporal or extratemporal onset. RESULTS--Regional hypometabolism occurred in 25 patients. Hypometabolic regions were ipsilateral to seizure onset and included lateral temporal (in 78% of patients), mesial temporal (70%), thalamic (63%), basal ganglial (41%), frontal (30%), parietal (26%), and occipital (4%). Specific patterns of temporal and extratemporal hypometabolism varied considerably across the TLE group. CONCLUSIONS--Any of the previously reported anatomic areas of hypometabolism can occur in individual patients with TLE. The prevalence of thalamic hypometabolism suggests a pathophysiologic role for the thalamus in initiation or propagation of temporal lobe seizures or in the interictal cognitive dysfunction of TLE.

Adult↗

Antineoplastic activity and tolerability of a novel heterocyclic alkylphospholipid, D-20133.

Octadecyl-[2-(N-methylpiperidinio)ethyl]-phosphate (OMPEP, D-20133), a heterocyclic analogue of hexadecylphosphocholine (MIL), has been synthesized in an attempt to increase the therapeutic range of the parent compound. The antineoplastic activity of the novel alkylphospholipid was compared with that of MIL in dimethylbenz(a)anthracene-induced mammary carcinoma of the rat. Using tumors of different sizes and repeated daily doses as well as high single doses, we achieved marked remissions with either compound. However, the therapeutic range of OMPEP was broader than that of the parent drug. Furthermore, the emetic potential of OMPEP tested on ferrets was distinctly less pronounced than that of MIL. In vitro the new alkylphospholipid proved to be more active than MIL in all cell lines tested, and its differentiation-inducing capacity turned out to be superior to that of MIL. No hematological toxicity was observed at various OMPEP doses during a 3-week treatment period.

9,10-Dimethyl-1,2-benzanthracene↗

Antitumour activity of miltefosine alone and after combination with platinum complexes on MXT mouse mammary carcinoma models.

Miltefosine, an alkylphosphocholine structurally related to alkyllysophospholipids showed highly selective antitumour activity against the hormone-sensitive variant of the s.c. transplantable MXT mouse mammary adenocarcinoma, the ovary-dependent MXT (M3.2), whereas it was inactive against the hormone-insensitive MXT (M3.2) OVEX variant. A dose of 32 mg/kg miltefosine p.o. daily for 5 weeks was well tolerated. Histopathological evaluation gave no signs of gastroenteral toxicity. After therapy the microarchitecture of the MXT (M3.2) tumours changed from that of a moderately differentiated adenocarcinoma to that of an anaplastic mammary carcinoma. A dose of 16 mg/kg miltefosine p.o. daily, though in effective per se, enhanced the antitumour activity of suboptimal i.p. doses of cisplatin and the hormone-like platinum analogue meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl) ethylenediamine]dichloroplatinum(II). Furthermore, it was shown, that miltefosine exhibited no (anti)hormonal properties. However, the mechanism of action of miltefosine remains unclear.

Adenocarcinoma↗

Minimal tourniquet pressure to maintain arterial closure in upper limb surgery.

Complications of the pneumatic tourniquet used during limb surgery result from excessive direct pressure. Traditional recommendations suggests parameters for maximum pressure and time limits rather than the minimal effective pressure to achieve a bloodless field. A clinical study was undertaken to evaluate the pneumatic tourniquet setting required for adequate haemostasis in the upper limb. The correlations between several possible influencing parameters (age, sex, arm fat thickness, extremity length, systolic, diastolic, and mean blood pressures) and the minimal pneumatic tourniquet pressure at which the peripheral pulse reappeared were studied in 50 patients undergoing surgery, using a Doppler stethoscope. The average Doppler Opening Pressure was 168.5 +/- 42.7 mmHg and the only significant clinical variable was the mean blood pressure. From these results an equation was derived to predict the minimal effective tourniquet pressure. The mean calculated tourniquet pressure was 202.3 +/- 34.2 mmHg, well below the 250 to 300 mmHg previously recommended. The technique consisted of inflating the tourniquet to a pressure of 300 mmHg, then reducing it to the calculated value. A bloodless field was maintained in all patients.

Adolescent↗

Characterization of mu opioid receptor binding during amygdala kindling in rats and effects of chronic naloxone pretreatment: an autoradiographic study.

Using in vitro autoradiography, mu receptor binding in rat brain was characterized at different amygdala kindling stages and in amygdaloid kindled animals pretreated chronically with naloxone. Male Sprague-Dawley rats implanted with bipolar electrodes in the right amygdala received one of the following pretreatments s.c. for 14 days via osmotic minipumps: normal saline solution, 0.5 microliters/h, or naloxone HCl, 75 micrograms/h. Two days after treatments were accomplished animals were stimulated daily. Our data showed different patterns of mu receptor binding during the normal kindling process: during stage II-III, pronounced binding increase was detected in cingulate, temporal and entorhinal cortices, anterior amygdala, caudate putamen, thalamic nuclei, ventrolateral and dorsolateral portions of central gray, substantia nigra pars compacta and pars reticulata. Twenty-four hours after the last stage V kindled seizure, enhanced binding was observed in cingulate and frontoparietal cortices, anterior amygdala, caudate putamen and ventromedial thalamic nucleus. Twenty-eight days after the last stage V kindled seizure, binding augmentation was noticed in cingulate and frontoparietal cortices, whereas decreased binding was detected in amygdala complex, substantia nigra pars reticulata, piriform, perirhinal, parietal, temporal and entorhinal cortices. Mu receptor binding in kindled rats chronically pretreated with naloxone was significantly higher in several structures when compared with control and normal kindled groups. Our data indicate different regional selective patterns of mu receptor binding during amygdala kindling which may depend on epileptogenesis and long-term changes induced by this process. In addition, even higher mu receptor binding results from chronic naloxone administration prior to kindling.

Amygdala↗

Intracerebral recordings: organization of the human epileptogenic region.

Intracranial recordings from patients with medically refractory partial epilepsy have demonstrated that the concept of a discrete epileptic focus, as derived from experiments with animals, does not exist in this human condition. Furthermore, an EEG spike focus, as defined by electroencephalographers, does not faithfully identify the site of ictal onset. Rather, the boundaries of an epileptogenic region, which is necessary and sufficient for generation of habitual spontaneous seizures, must be approximated by knowledge of the spatial distribution of interictal spike discharges, and ictal onset, as well as the location of an epileptogenic lesion demonstrated by structural imaging, and the location and extent of nonepileptic focal functional deficits. Delineation of an epileptogenic region is confounded by the fact that epileptically and nonepileptically abnormal brain tissue also exists beyond this area and may even involve the contralateral hemisphere. Investigations of epileptic patients during the course of surgical treatment have led to an improved understanding of the persistent neuronal disturbances that predispose to the generation of spontaneous seizures, as well as disturbances in adjacent and distant tissues that receive ictal propagation and demonstrate interictal epileptiform and nonepileptiform abnormalities. The results of such studies will greatly enhance our ability to interpret scalp-recorded EEG transients and to devise better, noninvasive, diagnostic tools to accurately define the epileptogenic region.

Brain↗

Cloning and characterization of the RNA polymerase alpha-subunit operon of Chlamydia trachomatis.

We have cloned the chlamydial operon that encodes the initiation factor IF1, the ribosomal proteins L36, S13, and S11, and the alpha subunit of RNA polymerase. The genes for S11 and alpha are closely linked in Escherichia coli, Bacillus subtilis, and plant chloroplast genomes, and this arrangement is conserved in Chlamydia spp. The S11 ribosomal protein gene potentially encodes a protein of 125 amino acids with 41 to 42% identity over its entire length to its E. coli and B. subtilis homologs; the gene encoding the alpha subunit specifies a protein of 322 amino acids with 25 to 30% identity over its entire length to its E. coli and B. subtilis homologs. In a T7-based expression system in E. coli, the chlamydial alpha gene directed the synthesis of a 36-kDa protein. Mapping of the chlamydial mRNA transcript by RNase protection studies and by a combination of reverse transcription and the polymerase chain reaction demonstrates that IF1, L36, S13, S11, and alpha are transcribed as a polycistronic transcript.

Amino Acid Sequence↗

Interictal heart rate patterns in partial seizure disorders.

Epileptogenic mesial temporal damage may alter interictal autonomic patterning. Analysis of heart rate variability in 19 patients with complex partial seizures revealed cases of persistent, high-amplitude, 4 to 9 per minute fluctuations in heart rate during alert waking. This pattern was most pronounced in poor candidates for anterior temporal lobe resection (2/19). The 4 to 9 per minute heart-rate variability pattern may emerge following diffuse, extratemporal, or bilateral mesial temporal damage, which interferes with descending forebrain influences on cardiovascular regulation.

Adolescent↗

Surgical treatment of partial epilepsy arising from the insular cortex. Report of two cases.

Despite its documented connections with many limbic structures, the role of the insula in the etiology of partial seizures is poorly understood. Two patients are described in whom lesions of the insula were associated with intractable partial seizures. In the first patient, the seizures involved visceral sensory hallucinations followed by motor automatism. Seizures in the second patient began with somatic sensory hallucinations and then produced visceral motor effects. Both patients were found to have low-grade astrocytomas of the insula. In both instances, resection of the lesion and adjacent insular cortex resulted in a cure of the seizures. These cases are placed within the context of the existing literature on the subject.

Adolescent↗

Clinical evaluation of interictal fluorine-18-fluorodeoxyglucose PET in partial epilepsy.

Interictal [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is useful in presurgical evaluation of medically refractory partial epilepsies. Limited replicability of image interpretation may restrict this application. We investigated interpretation replicability in 241 18F-FDG studies performed with three different tomographs in partial epilepsy patients. Two investigators independently interpreted the studies with a standardized evaluation protocol and without knowledge of the subjects. Replicability of these unbiased interpretations in detection of regional hypometabolism was best for studies performed with the highest performance tomograph. Interictal 18F-FDG studies performed with this tomograph revealed regional hypometabolism in 62% of patients who had normal cerebral magnetic resonance imaging (MRI). Replicability of interpretations in detecting regional hypometabolism was adequate for clinical application of interictal 18F-FDG studies performed with any of the tomographs.

Adolescent↗

[New central analgesic-acting triaminopyridines].

New Triaminopyridines with a Central Analgesic Activity 2-Amino-3-((prop-1-en-3-yl)oxycarbonylamino)-6-(4-fluorobenzyla mino) pyridine hydrochloride (D-19050) is a centrally and peripherally acting analgesic with rapid onset, long duration of action and a good therapeutic range. D-19050 can be obtained in a 5-step-synthesis starting from 2,6-dichloropyridine.

Aminopyridines↗

Single mossy fiber axonal systems of human dentate granule cells studied in hippocampal slices from patients with temporal lobe epilepsy.

Previous histological and immunocytochemical studies suggest that reorganization of the dentate granule cell axons, the mossy fibers, can occur in epileptic human hippocampus (Sutula et al., 1989; Houser et al., 1990; Babb et al., 1991) and in animal models of epilepsy (Tauck and Nadler, 1985; Sutula et al., 1988; Cronin et al., 1992). However, neuroanatomical analyses of the trajectory and morphology of reorganized axons are not yet available. The present study was conducted to investigate single dentate granule cell axonal systems in human epileptic hippocampus. Individual mossy fibers were directly visualized by injecting a tracer (biocytin or Lucifer yellow) intracellularly in hippocampal slices prepared from temporal lobes that were surgically removed from patients for treatment of intractable epilepsy. Two major arborization patterns were identified: (1) the parent axons extended to and coursed through the hilus toward CA3, leaving collaterals along their paths in the hilus (N = 19 neurons); (2) in addition to the aforementioned axonal system, collateral(s) branched from the parent axon near the soma and projected to the granule cell layer and molecular layer, forming an aberrant axonal pathway (N = 9 neurons). These aberrant collaterals bore large boutons similar to those of the hilar axons and formed extensive plexuses in the granule cell layer and/or in the molecular layer. The summed length of collaterals in the granular/molecular layers was 1110.8 microns on average, which was one-fourth of the total summed length of the mossy fibers (3698.5 microns on average). The size of the somata in neurons that had aberrant collaterals was significantly larger than that of neurons without such collaterals (p < 0.025). In four cases, filopodium-like fine processes were present near the axon hillock and proximal parts of the parent axon, suggesting that the aberrant collateral formation might be an ongoing process in these tissues. The lack of control slices from normal living human hippocampus makes it difficult to assess to what extent the present findings are epilepsy associated. However, the presence of aberrant mossy fiber collaterals in the hippocampi used in the present study has been confirmed by Timm's staining and/or dynorphin immunohistochemistry in comparison with nonepileptic autopsy material, indicating its relation to epilepsy (Babb et al., 1991, 1992). At present, there seems to be a consensus that the projection of mossy fiber collaterals to the supragranular layer is a rare occurrence in normal rats (Lorento de Nó, 1934; Claiborne et al., 1986; Seress et al., 1991; present study), normal monkeys (Seress et al., 1991), and normal humans (Houser et al., 1990).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Clinical neurophysiology, neuroimaging, and the surgical treatment of epilepsy.

Improved neurodiagnostic tools for examining cerebral structure and function have greatly enhanced the safety and efficacy of surgical treatment for epilepsy, and markedly increased the number of candidates for these surgical interventions. The application of new developments in clinical neurophysiology, as well as recent advances in neuroimaging, for surgical therapy of medically refractory seizures are reviewed. Improvements in surgical results are documented and future directions are discussed.

Cerebral Cortex↗