Biomedical subjects
Publications and source records attributed to J Engel.
An aneurysmal bone cyst (ABC) is an uncommon benign bone lesion that principally occurs in long bones and in the vertebral column. The appearance of ABC in carpal bones is very rare. We report a case of ABC that occurred in the hamate bone.
Stereoisomeric dichloro [1,2-bis(4-hydroxyphenyl)ethylenediamine]platinum(II) complexes (meso-3a, (+/-)-3b, (+)-3c, (-)-3d) and their N,N'-dibutyl derivatives (meso-4a, (+/-)-4b, (+)-4c, (-)-4d) were synthesized and tested on antitumor activity. The most active compound, 3d, shows a modest inhibition of the [3H]estradiol receptor interaction and causes a marked effect on the growth of the hormone-dependent human MCF 7 breast cancer cell line. It is also active on the hormone-independent human MDA-MB 231 breast cancer cell line, on the ADJ/PC6 plasmacytoma of the Balb/C mouse, and on the L 5222 leukemia of the BD IX rat. Apparently the inhibition of the MCF 7 cell line is not mediated by the estrogen receptor system. Histopathological studies on 3d revealed very low toxicity.
Know what is not epilepsy! An electroencephalographer can do much more damage by overinterpreting than by underinterpreting an EEG tracing. Epilepsy is a clinical, not an EEG, diagnosis, but the EEG, when used appropriately, can greatly aid the diagnostic process. Use activating techniques such as hyperventilation, photic stimulation, and natural sleep. Take advantage of seizures in the laboratory--this is a unique opportunity to make a diagnosis. If the ictal event is not accompanied by an EEG abnormality, and pseudoseizures are suspected, remember that patients with hysterical epilepsy often have real seizures as well. Use the EEG to help differentiate between generalized and partial epileptic conditions, and to identify benign epileptic syndromes. These diagnoses have important prognostic and therapeutic implications. The EEG can help determine whether a patient is deteriorating due to increased seizure activity (undermedicated) or increased side effects (overmedicated). Postictal slowing must be differentiated from progressive or drug induced changes. The best candidates for resective surgical therapy are otherwise healthy young adults with medically intractable partial complex seizures, no psychosis, and unilateral or bilaterally independent interictal anterior temporal EEG spike foci. Patients with multifocal or bilaterally synchronous interictal EEG spikes combined with mental retardation are less likely to benefit from resective surgery, although they may be helped by corpus callosum section.
Through the effective combination of instrumentation, tracer kinetic principles, and radiopharmaceuticals, positron computed tomography (PET) allows for the analytic, noninvasive measurement of local tissue physiology in humans. A large number of studies have already been performed in patients with epilepsy using 18F-fluorodeoxyglucose (FDG) to measure local cerebral glucose utilization. In patients with complex partial epilepsy who are candidates for surgery, hypometabolic zones have been seen consistently (70%) in the interictal state. These areas of hypometabolism have been related to electroencephalographic findings, surgical pathology, and clinical symptomatology. The complex anatomical and pathophysiological investigation of these hypometabolic zones is discussed. Ictal studies of patients with partial seizures have demonstrated a much more variable metabolic pattern which usually consists of hypermetabolism relative to baseline or interictal studies. Generalized epilepsy produced by electroconvulsive shock and petit mal epilepsy have been studied using FDG to estimate glucose metabolism. These studies demonstrated hypermetabolism in the ictal state, relative to interictal or postictal scans, but with a more generalized pattern than ictal studies of partial seizures. Methodological problems in the study of epilepsy with PET are discussed in detail. The investigation of interictal hypometabolism through animal models of epilepsy and quantitative autoradiography is described as a means to understand the human PET results. The impact and future direction of PET studies in epileptic populations will probably employ the use of behavioral, pharmacological, and electrophysiological maneuvers to provide more specific details about the fundamental pathophysiological mechanisms of specific aspects of epilepsy. These techniques may allow for a truly pathophysiological classification system for the common and unusual types of epilepsy, and through this classification system improve the therapeutic and prognostic clinical approach to patients.
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The locally subnormal brain metabolism observed in some experiments utilizing the Sokoloff 2-deoxyglucose (2-DG) method has often been attributed to postsynaptic inhibition despite the fact that inhibitory postsynaptic potentials are themselves caused by energy-requiring mechanisms. To explore this issue, neurophysiologically confirmed long-duration recurrent inhibition of hippocampal pyramidal unit firing was induced by low frequency (2 to 4 Hz) stimulation of the fornix for 60 min following intravenous infusion of [14C]-2-DG. The resulting autoradiograms showed that long-duration suppression of pyramidal cell firing was accompanied by distinctly increased hippocampal 2-DG uptake, particularly in the stratum pyramidale, which contains a dense plexus of inhibitory interneuronal terminals upon pyramidal cells. Both the pyramidal inhibition and the increased 2-DG uptake were confined to the ipsilateral hippocampus in animals with previously severed fornices and hippocampal commissures. In a second series of rats, the excitatory entorhinohippocampal "perforant path" (PP) was stimulated at low frequency (2 to 9 Hz) following 2-DG administration. At 2 to 4 Hz, each PP stimulation resulted in a brief burst of pyramidal unit firing followed by short-duration firing suppression; this result was associated with paradoxically decreased 2-DG uptake in the ipsilateral stratum molecular. By contrast, 7 to 9 Hz entorhinal stimulation induced PP-mediated excitation immediately followed by powerful intrinsic hippocampal inhibition, evidenced by prolonged pyramidal unit suppression after each stimulation. This suppression was accompanied by increased 2-DG uptake in the dentate stratum molecular and hippocampal stratum pyramidale. Thus it appeared that even with entorhinal stimulation, hippocampal 2-DG uptake was more closely associated with long-duration recurrent inhibition than with transient pyramidal excitation. Therefore, although it still remains possible that regions of hypometabolism observed in some previous 2-DG studies may actually reflect mild inhibition, other mechanisms such as disfacilitation are more likely mechanisms for this metabolic pattern.
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Intima collagen was studied by electron microscopy (rotary shadowing and negative staining) and by analytical ultracentrifugation. It was found that the monomeric unit (Mr 170 000) consists of a 105 nm-long triple helix terminated by a small globular domain (Mr about 30 000) at one end and a large globular domain (Mr about 40 000) at the other end. The monomer was produced by selective reduction of interchain disulphide bridges. Before reduction, dimers, tetramers and larger filamentous structures were found. Dimers are lateral staggered aggregates of two monomers aligned in an anti-parallel fashion. This gives rise to an inner 75 nm-long region of two slightly intertwisted triple helices flanked by the large globular domains. The outer triple-helical segments (length 30 nm) with the small globular domains at their ends emerge at both sides of this structure. Interchain disulphide bridges are probably located in the vicinity of the large domains. Only the outer segments could be degraded by bacterial collagenase. In tetramers the outer segments of two dimers are covalently linked, forming a scissors-like structure. In the fibrous forms several tetramers are assembled end-to-end with an overlap between the outer segments. The molecular masses and sedimentation coefficients were calculated for these various forms from the electron-microscopically observed dimensions and agreed with results obtained by ultracentrifugation. The unique structure of intima collagen suggests that it originates from a microfibrillar component and that it can be considered a unique collagenous protein, for which we propose the designation type VI collagen.
The effects of insulin on levels and turnover of catecholamines in the hypothalamus and medulla oblongata were investigated. Systemic or intraventricular administration of insulin had no effect on catecholamine levels, but increased the turnover rate of norepinephrine and epinephrine. Insulin induced a dose-related increased release of norepinephrine, epinephrine and dopamine from hypothalamic slices. These results indicate that the effects of insulin on central catecholamines are elicited by its action in the brain.
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Recurrent dislocation of the shoulder has long been recognized, and more than 100 techniques for repair of the injury are described. This survey describes 113 patients who suffered from recurrent anterior dislocation of the shoulder and were operated upon in accordance with the Putti Platt technique. The most significant preoperative finding was inadequate immobilization after the primary dislocation (62% of the patients). Postoperative recurrence was uncommon (1%) and a relative increased limitation of motion in the postoperative period improved gradually to almost a full range of movement.
The ontogenetic development of the audiogenic immobility reaction (freezing) was studied in rats given intracisternal injections of the neurotoxins 5,7-dihydroxytryptamine (5,7-DHT), 25 micrograms, or 6-hydroxydopamine (6-OHDA), 100 micrograms, neonatally (Day 1). The duration of the freezing response was strongly reduced in the 5,7-DHT-treated rats between 20-30 days of age, when normal animals show very prolonged responses. During the same period increased motor activity was observed in the 6-OHDA-treated rats while only a slight reduction of the freezing response was noted. Biochemical analyses performed on brains from animals 35 days of age showed a selective reduction (about 50%) of whole brain levels of serotonin in the 5,7-DHT-treated rats, while the noradrenaline levels were selectively reduced by about 60% in the 6-OHDA rats. A longitudinal investigation on the effects of neonatal treatment with 5,7-DHT showed a persistent selective reduction of the whole brain level of serotonin up to at least 90 days of age. Since 5,7-DHT mainly affects the serotonergic pathways, the results suggest that the disturbances noted in the ontogeny of the freezing response may be due to interference with the developing serotonergic system.
The effects of the enantiomers of 3-PPP on the maintenance of conditioned avoidance responding (CAR) were studied. The weak classical dopamine (DA) agonist (+)-3-PPP failed to interfere with CAR at any dose tested (0.8-13.6 mg/kg). Low doses of the drug produced sedation, while high doses produced behavioural stimulation. (-)-3-PPP, which acts as an antagonist on postsynaptic and as an agonist on autoreceptor DA sites, reduced avoidance with no effect on escape behaviour (6.8-13.6 mg/kg). However, this reduction of CAR occurred at doses much higher than those previously demonstrated to inhibit locomotor activity. This profile is discussed in relation to the behavioural effects of classical postsynaptic DA receptor antagonists.
The statistical properties of pre-ictal EEG spike activity in medial temporal lobe sites were analyzed in 6 patients with medically refractory complex partial seizures. A total of 24 1 h pre-ictal periods (2-6 periods per patient) were evaluated by quantifying the rate of occurrence of individual spatial patterns of spike activity derived from a subset (n = 6) of the recording channels. The channels chosen for analysis always included those medial temporal lobe sites which were documented to be most likely to initiate seizures, as well as their respective contralateral homologues. Each 1 h pre-ictal period was divided into 360 10 sec bins which were then visually classified into 1 of 64 possible spatial patterns of spike activity. These patterns, in turn, were grouped into 1 of 5 general spatial patterns and evaluated for trends across 3 20 min pre-ictal segments. Pooling these data across patients yielded the following results: (1) Focal patterns of spike activity tended to decline significantly in rate of occurrence several minutes prior to seizures, while the rate of independent contralateral patterns did not change. (2) The rate of occurrence of patterns of bilateral loosely coupled spike activity (involving focal and contralateral sites) increased significantly across the 20 min pre-ictal segments and was clearly augmented during the 20 min prior to seizures. These findings indicate that the degree of bilateral independence in medial temporal lobe spike activity tends to decrease several minutes prior to the localized onset of temporal lobe seizures; such changes may reflect the mechanisms responsible for the inter-ictal-ictal transition.
The ability of the CNS to generate seizures as a function of age was investigated utilizing the kindling model of epilepsy. Hourly electrical, low intensity stimulations of the amygdala induced kindling in adult rats, but stimulations delivered at 15 min intervals failed to or markedly retarded the development of kindled convulsions. In contrast, both types of stimulation induced consistent prolongation of the afterdischarges and repeated generalized seizures in suckling rat pups. The rate of development of the kindled convulsions in the pups was similar, irrespective of whether the stimulations were delivered at 15 or 60 min intervals, indicating that short (less than 15 min) seizure refractory periods exist in the immature brain. The data suggest that seizure susceptibility changes with age and is greater early in life.
Patients who were scheduled for surgical release of their trigger fingers underwent an injection of the involved tendon sheath prior to surgery. In thirty-six patients the injection of methylene blue was undertaken in a proximal-distal direction and in forty-three the direction of the injection was reversed. The success rate of the injections was 61 per cent. in the proximal distal group and 37 per cent in the second group. There was no significant statistical difference with regard to age, but duration of the disorder and mode of injection regarding the different fingers did have statistical significance.
A patient with partial complex seizures evaluated for surgery with chronic depth electrode recordings demonstrated falsely localizing ictal onsets during anticonvulsant drug withdrawal. When phenytoin was being reduced, more seizures appeared to originate from the left temporal lobe than from the right. Right anterior temporal lobectomy, performed on the basis of other findings, revealed a small unsuspected tumor in the resected specimen, and the patient has remained seizure free for 3 years. The seizures that originated from the left temporal lobe were different from the patient's habitual attacks and appeared to be the result of anticonvulsant withdrawal and, perhaps, electrode irritation. Four other patients who received anterior temporal lobectomies at UCLA between 1977 and 1980 had at least one stereotaxic EEG (SEEG)-recorded contralateral seizure onset, and all have benefited from surgery. Although multifocal SEEG-recorded ictal onsets should be considered a poor prognostic sign, distant sites that give rise to atypical seizures during drug withdrawal may not generate spontaneous seizures postoperatively. Consequently, this finding should not be used as a sole criterion against the recommendation of surgical therapy.