Biomedical subjects
Publications and source records attributed to J Engel.
This paper describes our diagnostic method, which enables an early and immediate differentiation between those patients who could benefit from a single or several local corticosteroid injections, and those who will probably require surgery. The authors have no intention of advocating a preferred treatment, but try to predict the outcome of the various modes of therapy.
Choline acetyltransferase (ChAC) measurement after complete transection of the sciatic nerve in rats revealed a steady increase in ChAC in the proximal nerve stump and a rapid drop in ChAC in the distal nerve stump. Ninety-six hours following transection no appreciable ChAC activity could be detected in the distal segment. The increase in the proximal segments was followed by a slight decline and leveling off at about twice the normal level. End-to-end nerve anastomosis, using the enzymatic nerve differentiation technique, could therefore be performed up to the first 96 hours. Nerve grafts could be used, with markedly improved results, up to the forty-fifth day following transection.
Interictal and ictal EEG characteristics derived from limited surface montages and medial temporal lobe sites were compared with long-term seizure relief following anterior temporal lobectomy in 52 epileptics. Patients were classified into one of four surgical outcome groups, ranging from seizure free to no clinical improvement. For each patient, interictal records were analyzed according to deep and surface spike characteristics and background activity. Ictal records were analyzed according to the proportion of episodes initiated in a unilateral or bilaterally synchronous fashion, the proportion of surface or deep onsets, the variability of onset location, and the morphology of seizures onsets. Interictal EEG variables that correlates with surgical outcome included: (a) various types of bilaterally synchronous surface/deep spikes; (b) diffuse background slowing; (c) sharp waves; and (d) the presence of multiple independent deep spike patterns in the lobe chosen for resection. Relevant ictal EEG variables included: (a) episodes initiated in a bilaterally synchronous fashion; (b) variability in seizure onset location; (c) the proportion of precisely focal onsets from deep sites; (d) the proportion of surface onsets; and (e) the proportion of onsets from the side chosen for resection. Multivariate analysis of these data with linear, stepwise, discriminate analysis and adaptive, nonlinear, distribution-free pattern recognition demonstrated that: (a) both interictal and ictal EEG characteristics can independently predict surgical outcome at levels significantly better than chance; (b) ictal and interictal EEG data contain nonredundant information for making such predictions; and (c) nonlinear pattern recognition techniques are capable of deriving the most accurate rules for predicting the effects of surgery.
Interictal and ictal characteristics of preoperative EEG recordings, derived from limited surface montages, and medial temporal lobe sites, were compared with the results of pathological studies done on resected lobes obtained from 44 patients with complex partial seizures. Pathological material was divided into four groups: (a) sclerosis (mesial temporal or restricted to pes hippocampi); (b) neoplasia (mainly hamartomas); (c) miscellaneous lesions; and (d) no significant lesions. Interictal EEG correlates of no pathology included bilaterally synchronous surface spikes (with or without simultaneous deep spikes) and independent surface spikes (with or without simultaneous deep spikes) on the sides of lobectomy. Ictal EEG correlates of no pathology included unilateral surface or surface/deep onsets, bilaterally synchronous surface onsets, more than one onset location, and suppression at onset. Focal onsets correlated with sclerosis. Frequent interictal spike activity in the nonlobectomized lobe and fast buildup at onset of ictus suggested neoplasia. Many of the EEG correlates of no pathology are known to correlate with poor postsurgical seizure relief, due probably in part to the fact that absence of pathology in the resected specimen is a negative prognostic sign. Patients with sclerosis could be distinguished from patients with no demonstrable pathology with 81% cross-validation classification accuracy using a distribution-independent, nonlinear classifier. Both interictal and ictal EEG measures were used by the classifier, and one may conclude that ictal and interictal EEG recordings contain nonredundant information for predicting the presence and type of underlying pathology.
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Positron computed tomography was used to investigate changes in the local cerebral metabolic rate for glucose (LCMRGlc) of the visual cortex. Progressive increases in LCMRGlc were found from eyes-closed control to stimulation with white light, alternating black/white checkerboard pattern, and a complex visual scene of a park, with the associative visual cortex increasing at a faster rate than the primary visual cortex as the visual scene complexity increased. A graded decrease in LCMRGlc of the visual cortex was found with a stepwise deletion of spontaneous cell firing at the retinal, geniculate and cortical level due to lesions. Left/right metabolic symmetry of the visual cortex during monocular stimulation confirms 50% crossing of the human visual system. Neonatal blindness showed no apparent degeneration of the visual cortex and was equivalent to eyes-closed controls. The interictal state of a patient with visual seizures demonstrated a hypometabolic visual cortex with a 2.5-fold increase in metabolism during an ictal visual hallucination.
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A new synthetic approach to the cerebroactive compound (+)-(R)-alpha-[(S)-1-[(3,3-di-3-thienylallyl)amino]ethyl]benzyl alcohol(1) (tinofedrine), its stereoisomers and related derivatives is reported. Several compounds increased blood flow in the arteriae vertebralis and femoralis of anesthesized dog.
We have developed a method of manipulation and external fixation of metacarpal fractures using Kirschner wires bonded with acrylic resin. This simple procedure requires no special instruments and it facilitates accurate reduction and stable fixation of the fracture while allowing free movement of the hand. Access to the wound is unhampered in open fractures. Thirty-six fractures were treated by this technique. All healed within five weeks, during which time free movement of the hand was encouraged. There were no complications.
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The binding of pure dimers, trimers and tetramers of randomly cross-linked non-immune rabbit immunoglobulin G to the first component and subcomponent of the complement system, C1 and C1q respectively, was studied. These oligomers possessed open linear structures. All three oligomers fixed complement with decreasing affinity in the order: tetramer, trimer, dimer. Complement fixation by dimeric immunoglobulin exhibited the strongest concentration-dependence. No clear distinction between a non-co-operative and a co-operative binding mechanism could be achieved, although the steepness of the complement-fixation curves for dimers and trimers was better reflected by the co-operative mechanism. Intrinsic binding constants were about 10(6)M-1 for dimers, 10(7)M-1 for trimers and 3 X 10(9)M-1 for tetramers, assuming non-co-operative binding. The data are consistent with a maximum valency of complement component C1 for immunoglobulin G protomers in the range 6-18. The binding of dimers to purified complement subcomponent C1q was demonstrated by sedimentation-velocity ultracentrifugation. Mild reduction of the complexes by dithioerythritol caused the immunoglobulin to revert to the monomeric state (S20,w = 6.2-6.5S) with concomitant loss of complement-fixing ability.
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Seventeen patients with partial epilepsy had electroencephalographic (EEG) monitoring concurrent with cerebral positron emission computed tomography (PECT) after 18F-fluorodeoxyglucose (18FDG) and 13N-ammonia (13NH3) were given intravenously as indicators of local cerebral glucose utilization (LCMRglc) and relative perfusion, respectively. In 12 of 15 patients who had unilateral or focal electrical abnormalities, interictal 18FDG scan patterns clearly showed localized regions of decreased (14 to 58%) LCMRglc that correlated anatomically with the eventual EEG localization. These hypometabolic zones appeared normal on x-ray computed tomography in all but 3 patients and were unchanged on 18FDG scans repeated on different days. In 5 of 6 patients who underwent anterior temporal lobectomy the interictal 18FDG scan correctly detected the pathologically confirmed lesion as a hypometabolic zone, and removal of the lesion site resulted in marked clinical improvement. In contrast, the ictal 18FDG scan patterns clearly showed foci of increased (82 to 130%) LCMRglc that correlated temporally and anatomically with ictal EEG spike foci and were within the zones of interictal hypometabolism (three studies in 2 patients). 13NH3 distributions paralleled 18FDG increases and decreases in abnormal zones, but 13NH3 differences were of lesser magnitude. When the relationship of 13NH3 uptake to local blood flow found in dog brain was applied as a correction to the patients' 13NH3 scan data, local alterations in perfusion and glucose utilization were usually matched in both the interictal and the ictal state. We conclude that the interictal 18FDG-PECT scan is useful in aiding localization of the dysfunctional cerebral zone most likely to be responsible for seizures in patients being considered for anterior temporal lobectomy. With further development, emission computed tomography may help in better categorizing the various forms of the disorder and in elucidating the basic mechanisms of epilepsy in humans.
Rabbit anti-SII pneumococcal polysaccharide IgG antibody was cross-linked by dithiobis (succinimidyl propionate). The IgG dimers were visualized by electronmicroscopy and resembled two Y-shaped structures connected in random orientations. The three arms of the Y's were of equal length. The six globular domains of the IgG protomers could be seen, but the Fab arms and Fc stems could not be distinguished from each other. Electron microscopy revealed that the dimers were bound to the globular heads of C 1 q. From the dependence of thee weight average molecular weight on dimer concentration, and equilibrium constant of about 10(6) M(-1) was derived for the binding of dimers to C 1 q. The number of IgG dimers which could be accommodated at a single C 1 q molecule was derived to be three. The data do not allow a clear distinction between noncooperative and cooperative binding. The binding equilibrium was independent of whether the IgG dimers were liganded with an SII nonasaccharide hapten or not. The results are at variance with an allosteric mechanism of the action of antigen in C1 activation. They lend support to the association hypothesis of complement activation. The data suggest that clusters of about six IgG molecules, connected by a multivalent antigen or arranged at the cell surface, are recognized by C 1 q with a binding constant of about 10(10) M(-1).
Rats were chronically treated with ethanol for 150 and 270 days, respectively. The influence of chronic ethanol treatment on the activation of tyrosine hydroxylation (measured as the accumulation of dopa after inhibition of amino acid decarboxylase) produced by gamma-butyrolactone (GBL) was studied. It appeared that the ability of GBL to enhance the dopa accumulation was attenuated in rats subjected to ethanol, thus indicating that subsensitivity will develop at or beyong GABA receptors following chronic ethanol treatment. Preliminary findings concerning the effects of chronic ethanol administration on dopamine autoreceptor sensitivity are also reported.
The effect of a single injection of various doses of lithium chloride was tested on conditioned avoidance behavior and on the accumulation of DOPA and 5-HTP after inhibition of aromatic amino acid decarboxylase. Lithium specifically suppressed conditioned avoidance behavior and reduced formation of DOPA, but not 5-HTP. The behavioral effect of lithium could be completely antagonized with additional L-DOPA treatment. The results indicate that lithium has a neuroleptlike effect on avoidance behavior, and it is suggested that some of the behavioral effects of lithium may be mediated via interference with central catecholaminergic mechanisms.