[Functional activity of autonomous adenoma in Germany]. / Funktionelle Aktivität fokaler Schilddrüsenautonomien in Deutschland.

BACKGROUND: The American (ATA) and the European Thyroid Association (ETA) recommend a thyroid scintiscan for the detection of a suspected autonomy only when serum thyrotropin (TSH) levels are low or suppressed. If ultrasound reveals a thyroid nodule > 1.0 cm and TSH is normal, a fine-needle biopsy is recommended without a preceding scintiscan as the next step. The aim of this prospective study was to evaluate the incidence of reduced or suppressed TSH in 100 autonomous adenoma > 1.0 cm and to clarify, if normal TSH does substantially exclude a focal autonomy. When the study was conducted no data of German patients were available. PATIENTS AND METHODS: An unselected group of 496 patients with a nodular goiter was continuously screened by scintiscan in order to detect 100 autonomous adenoma > 1.0 cm for the study. The following investigations were carried out: ultrasound, scintiscan and laboratory tests (fT3, fT4, TSH, TPO-antibodies). The reference range of TSH was 0.4 to 4.0 µU/ml. RESULTS: 21% of patients (100/476) with a nodular goiter had a focal autonomy. 32 % (32/100) of autonomous adenoma revealed a reduced (< 0.4 µU/ml) or completely suppressed TSH, while in 68 % (68/100) normal TSH level were found. CONCLUSION: In Germany autonomous adenoma are still frequent (21 % of all thyroid nodules). Most of them (68 %) reveal normal TSH levels. Our data demonstrate, that there is no relevant connection between TSH level and autonomous adenoma detected by scintiscan. In most cases, TSH is not able to discriminate, whether a nodule is autonomous or not. Biopsy of undetected autonomous nodules should not be performed, as they often show cytological features of follicular neoplasias. In thyroid nodules > 1.0 cm a scintiscan should routinely be performed in primary diagnostics to avoid unnecessary fine-needle biopsy of autonomous adenoma.

[Interventional endovascular therapy (stenting) for residual stenosis after lysis of the basilar artery]. / Interventionelle endovaskuläre Therapie (Stentimplantation) bei residuellen Stenosen nach Lyse der A. basilaris.

Despite the introduction of local thrombolytic therapy, there is still a very high mortality rate in basilar thrombosis. We report three cases of successful intra-arterial thrombolysis of acute basilar artery occlusion and consecutive interventional endovascular therapy. In all cases, the acute thrombosis of the basilar artery probably developed from preexisting atherosclerotic stenoses. The clinical outcomes were excellent. We discuss early consecutive stenting as a possible therapeutic option in cases of residual stenosis after successful intra-arterial lysis of basilar artery occlusion.

The effects of intra-amygdaloid infusions of a D2 dopamine receptor antagonist on Pavlovian fear conditioning.

The present study examined the effects of bilateral intra-amygdaloid infusions of the D2 receptor antagonist, eticlopride, on the acquisition and expression of Pavlovian fear conditioning as measured by freezing to acoustic and background contextual stimuli in the rat. Infusions of eticlopride before acquisition or before both acquisition and retention testing significantly attenuated conditioned freezing to tone presentations during the retention test 24 hr later. No effects, however, were observed on freezing that emerged during acquisition. Furthermore, these effects were not attributable to state-dependent learning effects or alterations in baseline activity or shock reactivity. In conclusion, these results suggest that amygdaloid dopamine transmission at D2 receptors contributes to the formation and/or consolidation of fear memories.

Arousal-related associative response characteristics of dorsal lateral geniculate nucleus neurons during acoustic Pavlovian fear conditioning.

This research determined whether fear-conditioned, acoustic stimuli induce thalamic arousal reflected in associative responses in dorsal lateral geniculate nucleus (dLGN) neurons. Rabbits received a Pavlovian discriminative fear conditioning procedure in which one tone conditioned stimulus (CS +) was always paired with an aversive unconditioned stimulus (US) and another tone (CS-) was never paired with the US. Responses of single dLGN neurons to random CS+ and CS- presentations were then recorded. Nine of 15 recorded neurons demonstrated significantly greater firing during the CS+ versus the CS-. Their spontaneous activity demonstrated tonic firing during increased neocortical arousal and burst firing during decreased neocortical arousal. The results demonstrate that dLGN neurons show associative responses to fear-conditioned, acoustic stimuli and present a model for investigating the neural circuits by which such stimuli affect sensory processing at the thalamic level.

An electrophysiological characterization of ventral tegmental area dopaminergic neurons during differential pavlovian fear conditioning in the awake rabbit.

Recent research has suggested that the mesencephalic dopaminergic (DA) system is activated by stress. For example, alterations in DA metabolites have been found in the ventral tegmental area (VTA) following footshock and immobilization in the rat [15,37]. Furthermore, this activation appears selective to DA neurons within the VTA since no changes were observed within the substantia nigra [15,16]. While this research suggests that DA neurons in the VTA are activated by aversive events, there has been a paucity of electrophysiological research designed to examine the sensory response characteristics of these DA neurons, and in particular their response to stimuli which predict aversive events. The present study was conducted to investigate the response characteristics of DA neurons within the VTA of the awake rabbit to acoustic stimuli which, via Pavlovian aversive conditioning procedures, came to predict the occurrence of a mild shock to the pinna. 45%, of the neurons meeting pre-established criteria for DA neurons demonstrated either significant excitation or inhibition to conditioned aversive stimuli. These neurons responded differentially to CS+ and CS- presentations. Some of these neurons (65%) demonstrated a greater increase in activity during the CS+ compared to the CS-, some (22%,) demonstrated a greater decrease in activity during the CS+ compared to the CS- and some (13%) demonstrated a greater increase in activity during the CS- compared to the CS+. Further, conditioned heart rate responses in the rabbits occurred during the recording of a majority of these neurons. These overall results suggest that conditioned aversive stimuli can affect the firing of VTA DA neurons and that these neurons comprise a heterogenous population with respect to their response profiles.

Amygdaloid D1 dopamine receptor involvement in Pavlovian fear conditioning.

The amygdala has long been implicated in conditioned fear. The mesencephalic dopaminergic system provides a rich innervation to the amygdala [J.H. Fallon, P. Ciofi, Distribution of monoamines within the amygdala, in: J.P. Aggleton (Ed.), The Amygdala: Neurobiological Aspects of Emotion, Memory and Mental Dysfunction, Wiley, New York, 1992, pp. 97-114; L.J. Freedman, M.D. Cassell, Distribution of dopaminergic fibers in the central division of the extended amygdala of the rat. Brain Research 633 (1994) 243-252; E. Asan, The catecholaminergic innervation of the rat amygdala. Advances in Anatomy Embryology and Cell Biology 142 (1996) 1-107]. Specific activation of the mesoamygdaloid dopaminergic system has been reported to occur in response to conditioned fear-arousing stimuli [M.L. Coco, C.M. Kuhn, T.D. Ely, C.D. Kilts, Selective activation of mesoamygdaloid dopamine neurons by conditioned stress: attenuation by diazepam. Brain Research 590 (1992) 39-47] suggesting that dopamine release in the amygdala may contribute to the acquisition and/or expression of conditioned fear. Using a 2x2 factorial design, Experiment 1A investigated the effects of bilateral intra-amygdaloid infusions of the selective D1 receptor antagonist, SCH 23390 (2.0 microgram 0.5 microliter-1 side-1), on the acquisition and expression of Pavlovian conditioned fear measured by freezing to acoustic and background contextual stimuli. Infusions of SCH 23390 prior to acquisition training, prior to retention testing or prior to both significantly attenuated conditioned freezing during retention testing. Experiment 1B investigated the dose-dependent effects of pre-training infusions of SCH 23390 (0.5, 1.0 and 2.0 microgram) on conditioned fear. Pre-training infusions of SCH 23390 dose-dependently attenuated conditioned freezing during retention testing. Experiment 2A investigated the effects of bilateral infusions of the selective D1 receptor agonist, SKF 82958 (2.0 microgram 0.5 microliter-1 side-1) on the acquisition and expression of conditioned fear. Infusions of SKF 82958 prior to training facilitated conditioned freezing during retention testing. Experiment 2B investigated the dose-dependent effects of pre-training infusions of SKF 82958 (1.0, 2.0 and 4.0 microgram) on conditioned fear. Pre-training infusions of SKF 82958 dose-dependently facilitated conditioned freezing during retention testing. In conclusion, these results suggest that dopamine transmission within the amygdala contributes to the acquisition and expression of Pavlovian fear conditioning.

Amygdaloid modulation of mesopontine peribrachial neuronal activity: implications for arousal.

This research sought to determine if activation of the amygdaloid central nucleus (ACe) modulates the activity of arousal-related neurons within the peribrachial (PB) region. Two categories of neurons were identified. Neurons of the 1st category demonstrated low spontaneous rates and responded with a burst of spikes to acoustic stimuli, characteristics similar to those reported for cholinergic ponto-geniculo-occipital (PGO) wave generator neurons. Neurons of the 2nd category demonstrated significant correlations between their spontaneous activity and the power of delta wave activity in the electroencephalogram (EEG) and responded to acoustic stimuli. Electrical stimulation of the ACe activated 43% of the PGO-related neurons but only 6% of the EEG-related neurons. The results suggest that the ACe modulates the activity of neurons that form the substrate for PGO waves, which are recognized correlates of arousal.

[Do low-threshold detoxification units reach new groups of the drug dependent?]. / Erreichen niedrigschwellige Entzugsstationen neue Gruppen von Drogenabhängigen?

The conventional form of detoxication for illicit drug users in German psychiatric hospitals is an inpatient treatment approach connected with high admission prerequisites. These demand a high stage of motivational compliance from of the patients, e.g. the determination to continue with long-term treatment aiming at a life free of drugs. This strategy is termed "high-threshold" approach. A new form of inpatient treatment is the "low-threshold" approach offering intervals of some days or weeks free of drugs to illicit drug users, supported by professional detoxication strategies. This study compares client characteristics of illicit drug users treated at "high-threshold" vs. "low-threshold" units. A new subpopulation of clients could be reached who are more advanced in their drug intake careers and less influenced by social pressure to enter treatment. The differences in clients treated can be explained rather by differences in admission prerequisites than by a more balanced distribution of sexes in the newly introduced detoxication programme.

Effect of lesions of the ventrolateral periaqueductal gray on the Pavlovian conditioned heart rate response in the rabbit.

The present experiment sought to evaluate the contribution of the ventrolateral periaqueductal gray to the expression of the conditioned bradycardic heart rate response in the rabbit. This response occurs in the presence of a fear-arousing conditioned stimulus. Lesions of the ventrolateral periaqueductal gray made after training failed to affect retention of the conditioned response. The results suggest that this region of the midbrain plays a nonessential role in the expression of the conditioned bradycardic response.

Fine structure of taste buds located on the lamb epiglottis.

BACKGROUND: Taste buds located on the aryepiglottal folds and laryngeal surface of the epiglottis are the principal receptors responsible for the initiation of the laryngeal chemoreflex. In contrast to the wealth of information available concerning the ultrastructure of oral taste buds, little comparable data exists for taste buds located at the entrance to the larynx. Therefore, the present study was designed to investigate the fine structure of taste buds located on the lamb epiglottis. MATERIALS: Stained thick and semi-serial thin sections from taste buds located on the lamb epiglottis were examined with light and electron microscopy. RESULTS: Based on morphological criteria, three types of cells could be identified in the taste bud: Type I, Type II, and basal cells. Both Type I and Type II cells extended into the apical taste pore, but there were differences between these two cell types with regard to nuclear profiles, electron density, and the relative density of ribosomes, apical mitochondria, and rough and smooth endoplasmic reticulum. Basal cells did not extend a process into the taste pore. Nerve processes were observed throughout the taste bud. Synapses were observed between both Type I and Type II cells and nerve fibers. These synapses exhibited membrane thickenings and accumulations of clear and dense-cored vesicles of varying proportions in the taste cell cytoplasm adjacent to membrane specializations. CONCLUSIONS: The taste buds located on the lamb epiglottis share several structural similarities to taste buds located in the oral cavity and other regions of the pharynx and larynx of many mammalian species. The presence of synapses on both Type I and Type II cells of the lamb epiglottal taste bud suggests that both cell types are involved in laryngeal chemoreception.

Neuronal activity within the nucleus basalis and conditioned neocortical electroencephalographic activation.

The relationship between neuronal activity within the nucleus basalis (NB) and conditioned neocortical EEG activation was investigated in New Zealand rabbits during Pavlovian differential conditioning. Twenty-seven of 56 neurons recorded in conditioned animals demonstrated a significantly greater change in activity to a tone (CS+) that predicted the occurrence of a mildly aversive unconditioned stimulus when compared to a tone (CS-) that did not. Twenty-four of these 27 neurons demonstrated a significant increase in activity to the CS+ compared to the CS-, while the remaining three neurons demonstrated a significant decrease in activity to the CS+ compared to the CS-. In 24 of these 27 neurons (89%) these changes in neuronal activity during CS presentations correlated significantly with a decrease in the power of delta activity in the EEG. In addition, 13 of these 24 neurons (54%) demonstrated significant correlations between neuronal activity and the power of delta activity during CS-free periods. In experimentally naive animals, the activity of 10 of 22 neurons (45%) recorded within the region of the NB correlated with the power of delta activity in the EEG during stimulus-free periods. These results complement a growing body of evidence and provide strong support for the hypothesis that the NB contributes to neocortical activation in the conscious animal.

Effects of electrical stimulation of the amygdaloid central nucleus on neocortical arousal in the rabbit.

This study sought to determine whether electrical stimulation of the amygdaloid central nucleus (ACe) produces cholinergically mediated neocortical arousal manifested in the suppression of frontal cortex delta wave (1-4 Hz) activity. Stimulation in both anesthetized and conscious rabbits produced a suppression of delta activity that was accompanied by bradycardia and blocked by cholinergic antagonists. Stimulation of the adjacent putamen did not produce delta suppression, whereas stimulation of the adjacent ventral globus pallidus produced a suppression of shorter duration than that produced by ACe stimulation. The results suggest that the ACe influences neocortical arousal, which may be mediated by its influence on the activity of cholinergic neurons of the nucleus basalis.

Anatomical and physiological relationships between the anterior cerebellar vermis and the pontine parabrachial nucleus in the rabbit.

The anatomical connections between the midline cerebellum and the pontine parabrachial nucleus (PBN) were investigated in the rabbit using anterograde and retrograde axonal transport techniques. Small injections (20-50 nl) of cholera toxin conjugated to horseradish peroxidase (CT-HRP) or wheat germ agglutinin conjugated HRP (WGA-HRP) into the cortex of the anterior cerebellar vermis resulted in retrograde and anterograde-like label in the PBN. Focal injections of tracer into the PBN resulted in anterogradely labeled processes in the ACV and retrogradely labeled a small, but distinct group of Purkinje cells within the anterior vermis. Focal injections into the rostral fastigial nuclei (FN) resulted in anterograde-like label in the PBN, and PBN injections labeled FN neurons. Furthermore, the projection from the PBN to ACV is effective in driving cerebellar neurons as electrical microstimulation of the PBN evoked short-latency, phasic responses in ACV Purkinje cells. These experiments generated anatomical and physiological evidence for the existence of a neuroanatomical circuit connecting the midline cerebellum (ACV, FN) with the PBN, that may serve as a functional interface between the midline cerebellum and other brain stem nuclei with cardiovascular function, particularly with respect to the midline cerebellar role in classically conditioned cardiovascular responses.

The anterior cerebellar vermis: essential involvement in classically conditioned bradycardia in the rabbit.

The effects of lesions of the cerebellum on the acquisition and retention of aversive Pavlovian conditioned bradycardia were examined in rabbits. Lesions of the anterior cerebellar vermis severely attenuated the acquisition of simple conditioned bradycardia without disrupting baseline heart rate (HR), or unconditioned HR responses. Also, lesions of the vermis performed after the acquisition of conditioned bradycardia eliminated evidence of prior conditioning. Bilateral lesions of the cerebellar hemispheres did not affect conditioned or unconditioned HR responses. These results were interpreted to indicate that anterior vermis lesions specifically disrupted part of an essential conditioned response pathway without interfering with the neural circuits that mediate unconditioned HR responding. These lesion data, coupled with recent electrophysiological evidence of learning-related changes in neuronal activity within the anterior vermis of the fear-conditioned rabbit, suggest that the anterior cerebellar vermis is critically involved in the acquisition and retention of this rapidly learned autonomic conditioned response.

Purkinje cell responses in the anterior cerebellar vermis during Pavlovian fear conditioning in the rabbit.

Extracellular single-unit recordings of Purkinje cells in the anterior cerebellar vermis (ACV) of the rabbit found evidence of short-latency (20-30 ms) differential responses to discriminatively-conditioned auditory stimuli during Pavlovian fear conditioning procedures. These differential unit responses appeared to be a function of learning as differential ACV Purkinje cell responses were not observed in naive (untrained) animals. Some of these evoked neurophysiological responses were also correlated with the behavioral conditioned autonomic response. (CAR); a conditioned bradycardiac response. These electrophysiological data, coupled with previous lesion results, suggest that the ACV is part of an important neural circuit for Pavlovian conditioned bradycardia.