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PubMed2005

Aggressive behavior of classical Kaposi's sarcoma and coexistence with angiosarcoma.

UNLABELLED: An 82-year-old Caucasian man presented with initially asymptomatic livid red plaques on the plantar surface of the feet that become confluent and evolved into invasively growing nodules accompanied by massive edema. Histology allowed a diagnosis of the classical form of Kaposi's sarcoma; the serology test result for HIV was negative, whereas the associated human herpes virus type 8 was detected by polymerase chain reaction on the skin sample. Over the subsequent 6 months, skin lesions become vegetative and partially necrotic, and extended to the hands and eyelids. Chemotherapy with vinblastine appeared to stabilize the cutaneous disease, but the patient developed a massive gastrointestinal hemorrhage secondary to dissemination to the stomach. Twelve months after the onset of the disease, vegetative and easily bleeding lesions progressively occluded the mouth of the patient: histological features were consistent with a low-grade angiosarcoma distinct from that of Kaposi's sarcoma. The patient could not chew and swallow anymore; he was put on an artificial nutrition but died shortly thereafter. This case illustrates that, even in its classical form, Kaposi's sarcoma may be a malignant, rapidly progressing tumor. LEARNING POINTS: a) The extent and rate of spread of initial skin lesions should be considered to be early signs of aggressive dissemination, even in the absence of other variables (i.e., histological pattern, human herpes virus type 8 positive mononuclear cells) associated with progression of the disease. b) An endoscopy may be useful given the high prevalence of gastrointestinal involvement. c) When classical Kaposi's sarcoma displays aggressive behavior a second, primary malignant tumor arising from the vascular tissue should be investigated. TAKE-HOME MESSAGE: Even in its classical form, Kaposi's sarcoma may be a malignant, rapidly progressing tumor with visceral involvement; also, a second malignancy may occur in nearly one patient of four. Because localized skin lesions can regress completely with radiotherapy, watchful waiting is probably inappropriate in most cases.

Aged↗

PubMed1999

[Problem-based teaching and learning. An opportunity for medical psychology, psychosomatic medicine and psychotherapy?].

All proposals for a reform of the study of medicine recommend problem-based teaching and learning methods. The rapid increase in the number of medical faculties abroad offering experimental courses along these lines is an indicator of their usefulness. The results of empirical research also suggest that departments of medical psychology, psychosomatic medicine and psychotherapy should participate more closely in the introduction and exploration of the advantages of this didactic approach.

Problem-Based Learning↗

PubMed2000

Rapid and selective induction of BDNF expression in the hippocampus during contextual learning.

The hippocampus is required for many forms of long-term memory in both humans and animals, and formation of long-lasting memories requires the synthesis of new proteins. Furthermore, the long-term potentiation (LTP) of hippocampal synapses, a widely studied model of memory, also depends on both de novo gene transcription and protein synthesis and results in the activation of transcription from promotors containing the cAMP response element (CRE). Expression of several genes is induced during the establishment of LTP; these include the immediate-early genes (IEGs) BDNF (brain-derived neurotrophic factor), zif268 and C/EBPbeta (CCAAT-enhancer binding protein beta), all of which contain CRE sites within their promotor regions. However, these genes induced by LTP are not known to be rapidly induced following learning in a natural setting. Here we demonstrate rapid and selective induction of BDNF expression during hippocampus-dependent contextual learning.

Amygdala↗

PubMed2006

The effect of N-methyl-D-aspartate receptor blockade on acetylcholine efflux in the dorsomedial striatum during response reversal learning.

Separate experiments found that activation of N-methyl-d-aspartate (NMDA) receptors or increased acetylcholine (ACh) efflux in the rat dorsomedial striatum is critical for learning when conditions require a shift in strategies. Increasing evidence indicates that NMDA receptor activity affects cholinergic efflux in the basal ganglia. The present studies determined whether NMDA receptor blockade in the dorsomedial striatum with dl-2-amino-5-phosphonopentanoic acid (AP-5) affects dorsomedial striatal ACh output in a resting condition, as well as during response reversal learning. Experiment 1 investigated the effects of AP-5 (12.5, 25 or 50 muM) infused into the dorsomedial striatum on ACh output in a resting condition. AP-5 infusion at 25 and 50 muM led to a 20% and 40% decrease in dorsomedial striatal ACh output, respectively. AP-5 (12.5 muM) infusion did not change dorsomedial striatal ACh output from basal levels. Experiment 2 determined whether dorsomedial striatal ACh efflux increases during response reversal learning and whether AP-5, at a dose that does not affect basal levels, modifies response reversal learning and ACh efflux. Following acquisition of a response discrimination, rats had microdialysis probes bilaterally inserted into the dorsomedial striatum prior to the reversal learning test. After baseline samples, rats received a response reversal learning test for 30 min. Control rats rapidly improved in the reversal learning session while simultaneously exhibiting an approximately 40% increase in ACh output compared with baseline levels. AP-5 (12.5 muM) treatment during testing significantly impaired response reversal learning while concomitantly blocking an increase in ACh output. These findings suggest that NMDA receptor activation in the dorsomedial striatum may facilitate a shift in response patterns, in part, by increasing ACh efflux.

2-Amino-5-phosphonovalerate↗

PubMed2005

Dopamine cells respond to predicted events during classical conditioning: evidence for eligibility traces in the reward-learning network.

Behavioral conditioning of cue-reward pairing results in a shift of midbrain dopamine (DA) cell activity from responding to the reward to responding to the predictive cue. However, the precise time course and mechanism underlying this shift remain unclear. Here, we report a combined single-unit recording and temporal difference (TD) modeling approach to this question. The data from recordings in conscious rats showed that DA cells retain responses to predicted reward after responses to conditioned cues have developed, at least early in training. This contrasts with previous TD models that predict a gradual stepwise shift in latency with responses to rewards lost before responses develop to the conditioned cue. By exploring the TD parameter space, we demonstrate that the persistent reward responses of DA cells during conditioning are only accurately replicated by a TD model with long-lasting eligibility traces (nonzero values for the parameter lambda) and low learning rate (alpha). These physiological constraints for TD parameters suggest that eligibility traces and low per-trial rates of plastic modification may be essential features of neural circuits for reward learning in the brain. Such properties enable rapid but stable initiation of learning when the number of stimulus-reward pairings is limited, conferring significant adaptive advantages in real-world environments.

Action Potentials↗

PubMed2004

Age-of-acquisition effects in reading aloud: tests of cumulative frequency and frequency trajectory.

Several studies have reported that the age at which a word is learned affects skilled reading. This age-of-acquisition effect is potentially important for theories of reading and learning. The effect has been difficult to pin down, however, because the age at which a word is learned is correlated with many other lexical properties. Zevin and Seidenberg (2002) analyzed these phenomena, using connectionist models that distinguished between cumulative frequency (the total number of times a word is experienced) and frequency trajectory (the distribution of these experiences over time). The models prompted a reevaluation of the empirical literature on this topic. The present research tested and confirmed three behavioral predictions derived from these models. First, cumulative frequency has an impact on skilled word naming, more so than standard measures of frequency derived from such norms as those of Kucera and Francis (1967). Second, frequency trajectory affects age of acquisition: The timing of exposure to words affects how rapidly they are learned. However, frequency trajectory does not affect skilled reading aloud, because the consistencies in mapping between spelling and sound eventually wash out the effects of early differences in frequency of exposure. Thus, in skilled performance, the timing of exposure to words is less important than the amount of exposure. The results clarify the conditions under which age-dependent learning effects occur in reading aloud.

Adolescent↗

PubMedDate not supplied

Chunking by a pigeon in a serial learning task.

A basic principle of human memory is that lists that can be organized into memorable 'chunks' are easier to remember. Memory span is limited to a roughly constant number of chunks and is to a large extent independent of the amount of informaton contained in each chunk. Depending on the ingenuity of the code used to integrate discrete items into chunks, one can substantially increase the number of items that can be recalled correctly. Newly developed paradigms for studying memory in non-verbal organisms allow comparison of the abilities of human and non-human subjects to memorize lists. Here I present two types of evidence that pigeons 'chunk' 5-element lists whose components (colours and achromatic geometric forms) are clustered into distinct groups. Those lists were learned twice as rapidly as a homogeneous list of colours or heterogeneous lists in which the elements are not clustered. The pigeons were also tested for knowledge of the order of two elements drawn from the 5-element lists. They responded in the correct order only to those subsets that contained a chunk boundary. Thus chunking can be studied profitably in animal subjects; the cognitive processes that allow an organism to form chunks do no presuppose linguistic competence.

Animals↗

PubMed1997

Experimental field study of spatial memory and learning in wild capuchin monkeys (Cebus capucinus).

Despite a large body of data on diet and ranging patterns in prosimians, monkeys and apes, little is known regarding the types of information that non-human primates use when making foraging decisions. In a series of controlled field experiments, we tested the ability of wild capuchins (Cebus capucinus) at La Suerte Biological Research Station in north-eastern Costa Rica to remember the spatial positions of 13 feeding platforms and use olfactory and visual cues to identify baited (real bananas) versus sham (plastic bananas) feeding sites. The results indicate that when 'place' was predictable, the capuchins learned the spatial locations of food and non-food sites rapidly (one-trial learning). In a second experiment, the positions of baited feeding sites were random. In the absence of other information, the capuchins used the presence of a local landmark cue (yellow block) placed at reward platforms to select feeding sites. In a final experiment, there was evidence that expectations regarding the amount of food available at a platform (2 bananas vs. 1/2 banana) had a significant influence on capuchin foraging decisions. Although the capuchins were sensitive to changes in experimental conditions, when they were given conflicting cues, spatial information was predominant over other information in selecting feeding sites.

Animals↗

PubMed1997

Highest level automatisms in the nervous system: a theory of functional principles underlying the highest forms of brain function.

A concept that all hierarchical levels of the nervous system are built according to the same functional principles is proposed. Each level is responsible for a discrete type or set of automatisms, is a learning system, and contains two distinct functional subdivisions: (1) a controller, a subsystem providing a governing set of rules or commands-a control law-that directs the action of the recipient of these rules-the controlled object; and (2) a model, a subsystem that generates a model of object behavior, i.e. afferent information flow expected from the controlled object. A control system such as this receives two types of afferent signals-initiating and informational. The difference between these signals is that a control system minimizes initiating signals during the realization of an automatism, i.e. a control neural network utilizes informational signals to compute the proper output that minimizes the initiating input signal. A mismatch or error signal, a type of initiating signal, is responsible for learning. Both the control law and the model can be adjusted during learning. The learning process starts when the error signal increases and stops when it is minimized. A network hierarchy is structurally and functionally organized in such a way that a lower control system in the nervous system becomes the controlled object for a higher one. This hierarchy leads to a generalization of encoded functional parameters and, consequently, the working space for each higher level control system becomes more abstracted. This is the reason why each hierarchical level within the control nervous system uses detectors specific for feature of the controlled object and the environment that match the control needs in order to obtain information about the current state of the object in the environment. Movement of information toward higher hierarchical levels also is accompanied by an increase in the duration of initiating signals within each control system. The ability to store a long prehistory of preceding events is considered as the mechanism that necessitated the invention of more complex and more rapid forms of learning such as operant learning, and made possible more complex multistep computational algorithms that require memorization of the results of previous intermediate computations. The functions of the cerebellum, the limbic system and the cortico-basal ganglia-thalamocortical loops are analyzed to illustrate the utility and applicability of this theoretical concept. Basal ganglia-thalamocortical loops are described as modeling, predictive loops, and their dopaminergic innervation as an error distribution system.

Automatism↗

PubMed2005

Glucose regulation of memory for reward reduction in young and aged rats.

Although baseline blood glucose levels in aged Fischer-344 rats are comparable to those of young rats, the rise in blood glucose in response to training-related stress is substantially attenuated. The diminished response may contribute to increased depletion of extracellular brain glucose levels during training in aged rats; the depletion is blocked and memory is enhanced by systemic injections of glucose. The present experiment examined the role of glucose in regulating memory for reward reduction training. Blood glucose levels exhibited a significant rise after reward reduction trials in young adult but not 2-year-old rats. Although young and aged rats exhibited comparable learning during the day of reward reduction training, aged rats exhibited more rapid forgetting of the learning response. Post-training glucose injections (200 mg/kg, i.p.) facilitated memory formation and slowed the rate of forgetting in young and old rats, consistent with the view that deficiencies in circulating glucose responses to training may contribute to the rapid forgetting evident in aged Fischer-344 rats.

Aging↗

PubMed2006

Early experience and domestication affect auditory discrimination learning, open field behaviour and brain size in wild Mongolian gerbils and domesticated laboratory gerbils (Meriones unguiculatus forma domestica).

The influence of early experience and strain differences on auditory discrimination learning, open field behaviour and brain size was investigated in wild-type Mongolian gerbils (strain Ugoe:MU95) raised in the wild (wild F-0) or in the laboratory (wild F-1) and in domesticated Laboratory Gerbils (LAB). Adult males were conditioned for 10 days in a shuttle box go/no-go paradigm to discriminate two frequency-modulated tones. Significant learning was established within 5 days in wild F-0 and within 3 days in wild F-1 and LAB. Spontaneous jumps in the shuttle box (inter-trial crossings) were frequently seen in wild F-0 and F-1, but rarely in LAB. All groups exhibited nearly the same ability to remember after 2 weeks without training. In the open field test applied on 5 consecutive days, no differences in locomotion patterns and inner field preferences were found. Rearing frequency decreased over 5 days in wild gerbils. Running distances (4-6m/min) were similar in wild F-0 and LAB, but higher in wild F-1. The ratio of brain size to body weight did not differ between wild F-0 and F-1, but was 17.1% lower in LAB. Correspondingly high brain weights in wild F-1 and F-0 support our domestication hypothesis and negate any serious effect of early experience or captivity on brain size in Mongolian gerbils. In contrast, wild F-1 raised in the laboratory show a rapid improvement in learning performance, indicating that early experience rather that genetic differences between strains affect shuttle box discrimination learning in gerbils.

Acoustic Stimulation↗

PubMed2004

Results with titanium ossicular reconstruction prostheses.

OBJECTIVES/HYPOTHESIS: Despite the enthusiasm of recent short-term reviews, no center in the United States has published results meeting American Academy of Otolaryngology-Head and Neck Surgery guidelines with titanium-based prostheses. The purpose of the study was threefold. The first purpose was to review results with a titanium prosthesis system in cases meeting American Academy of Otolaryngology-Head and Neck Surgery reporting guidelines. The second was to compare these results with previously published results using non-titanium-based prostheses. The third was to examine the authors' results for any evidence of a "learning curve." STUDY DESIGN: Retrospective chart review was performed for the period from February 2000 to August 2001 and for the period from July 2002 to February 2003. METHODS: Of 313 cases, 130 consecutive cases were identified in the first period and 65 in the second time period. One hundred two patients had adequate follow-up for published guidelines. All cases were performed by the senior author (c.g.j.). Comparison data were obtained from a previous publication involving the senior author. RESULTS: Successful rehabilitation (<or=20 dB pure-tone average air-bone gap) of conductive hearing loss was obtained in 70% of partial ossicular chain reconstructions and 44% of total ossicular chain reconstructions when titanium prostheses were used. Comparison data revealed successful rehabilitation in 48% and 21% of non-titanium-based partial and total reconstructions, respectively. Postoperative pure-tone average air-bone gaps were not significantly different when compared with results in the period from July 2002 to February 2003. CONCLUSION: Newer titanium-based ossicular reconstruction devices represent an improvement over previously used non-titanium-based prostheses. The authors think that this improvement is realized rapidly because no learning curve existed in their data.

Bone Conduction↗

PubMed2004

[Web-based training in radiology - student course in the Virtual University of Bavaria].

PURPOSE: The ninth version of the licensing regulation for medical doctors (Approbation Regulation (AR)) sets a benchmark in terms of practical experience, interdigitation of preclinical and clinical studies, interdisciplinary approach, economic efficiency, independence of students, added new teaching and learning modalities, and ongoing evaluation of the progress of the medical students. It is the aim to implement these major points of the AR in a model course for diagnostic radiology and radiation protection within the scope of the Virtual University of Bavaria and test them in practice. MATERIALS AND METHODS: In cooperation with residents and board certified radiologists, students developed the virtual course "Web-Based Training (WBT) Radiology" in diagnostic radiology and radiation protection for students in the first clinical semester. A representative target group taken from the student body was asked about the options to get access to the World Wide Web (Internet), and the satisfaction concerning configuration and content of the newly developed program. A comparison was made between the results of the final examination taken by students who made use of the virtual course in addition to conventional lessons and taken by students who did not subscribe to the virtual course and exclusively relied on conventional lessons. In addition, a pilot study was conducted in the winter semester 2002/03, which compared students taking either the traditional lessons or the new virtual course on the Internet. RESULTS: The virtual course-model had test results with a positive trend. All targeted students had Internet access. Constructive criticism was immediately implemented and contributed to rapid optimization. The learning success of the additive or alternative virtual course was in no way less than the learning success achieved with the conventional course. CONCLUSION: The learning success as measure of quality in teaching and the acceptance by students and teachers justify the continuation of this course model and its expansion. Besides enabling the learning in small study groups; the course "WBT Radiology" might not only help implementing the major points of the new AR but might also complement any deficiencies in the current education. Economic aspects may encourage their implementations.

Computer-Assisted Instruction↗

PubMed1991

Decreased glutamate release correlates with elevated dynorphin content in the hippocampus of aged rats with spatial learning deficits.

The effects of aging on extracellular glutamate and tissue dynorphin content in the hippocampus were examined in Fischer-344 rats. Young adult (4-month-old) and aged (24-month-old) rats were trained to find a hidden platform in the Morris water task. Aged rats were unable to acquire the spatial learning task as rapidly as young controls. Following behavioral testing, an in vivo microdialysis perfusion method was used to determine extracellular glutamate levels in the hippocampus. There was a 25-35% reduction in extracellular glutamate concentration in both dorsal and ventral hippocampus of aged rats compared to young rats, in the absence of any change in tissue glutamate levels. Radioimmunoassay showed an increase in dynorphin A(1-8)-like immunoreactivity [DYN-A(1-8)LI] in both dorsal and ventral hippocampus, but not striatum, of aged rats. Immunocytochemistry indicated that this increase was localized to the dentate granule cells and mossy fibers. Furthermore, among the aged rats the increase in DYN-A(1-8)LI was inversely correlated with the decrease in extracellular glutamate. These results suggest that the disregulation of dynorphin observed in cognitively impaired aged rats is related to reduced excitatory transmission within the hippocampal formation.

Aging↗

PubMed1989

An analysis of several variables influencing the efficacy of flash card instruction.

We conducted four experiments using an alternating treatments design to assess the influence of several variables on children's acquisition of number facts during one-on-one flash card instruction. In Experiment 1, we manipulated the order of stimulus presentation; in most cases a higher percentage of correct responses occurred, and mastery criterion was reached in somewhat fewer sessions, when a missed problem was re-presented after the next item than when problems were re-presented in a sequential order. In Experiment 2 a comparison of error-contingent reprimands with no reprimands yielded similar results in favor of the former procedure. Experiment 3 indicated that a higher percentage of correct responses and more rapid acquisition occurred when the tutor and student were seated knee-to-knee than when a desk was positioned between them. Experiment 4 compared the rate of learning in the presence and absence of a treatment package consisting of all three variables identified as leading to more rapid learning in the previous three experiments. Children reached criterion in less than half the time when the treatment package was in effect.

Journal Article↗

PubMed1979

The spouse as facilitator for esophageal speech: a research perspective.

The role of the spouse in relation to the quality of esophageal speech of laryngectomized patients was investigated using psychodiagnostic instruments and speech ratings and through an assessment of the verbal interactions between the patient and spouse. Analysis of the results indicates that those speakers who were objectively judged to have higher quality speech and learned esophageal speech rapidly had spouses who were more likely to disagree verbally with them, addressed them in a way that encouraged long answers, and evidenced reciprocal compatibility for meeting affectional needs.

Aged↗

PubMed1991

On the pharmacological phenocopying of memory mutations in Drosophila: alkylxanthines accelerate memory decay.

Theophylline and 3-isobutyl-1-methylxanthine, two cyclic nucleotide phosphodiesterase inhibitors, when fed to wild-type Drosophila adults, cause the rapid decay of learning index after training in a shock-odor learning paradigm. The drugs practically do not affect the olfactory acuity of flies, hence they influence the learning/memory process itself. The time courses of memory decay resemble those of the memory mutants rutabaga and amnesiac and, to a lesser extent, dunce2 and dunceM11. Theophylline further deteriorates the learning performance of dunceM11. Biochemical characterization of the inhibition of the two major phosphodiesterase isoenzymes in Drosophila by theophylline predicts only a slight inhibition of these enzymes in vivo, in accordance with the unchanged level of cAMP in wild-type fly heads during drug feeding. 8-Phenyltheophylline, an adenosine receptor antagonist in mammals, slightly retards memory decay in the wild-type. It is suggested that alkylxanthines induce memory decay in Drosophila by interfering with cAMP dynamics at more than one point of its metabolism.

1-Methyl-3-isobutylxanthine↗

PubMed2004

Free operant and discrete trial performance of mice in the nine-hole box apparatus: validation using amphetamine and scopolamine.

RATIONALE: To determine the suitability of the nine-hole box to characterise mouse performance on a free operant task and a discrete trials task, and to validate the tests by probing whether d-amphetamine and scopolamine modify performance of the task as predicted. OBJECTIVES: To demonstrate the functionality and efficiency of the mouse nine-hole box for the evaluation of performance under fixed- (FR) and progressive-ratio (PR) operant schedules, as well as under a three-choice visual discrimination task and subsequent reversals of the task. In addition, sensitivity of the apparatus was assessed using pharmacological challenges. METHODS: C57BL/6J were tested on CRF, FR5, FR10, FR20, and a modified PR3 schedule. Behavioural response to d-amphetamine sulphate (0.1, 0.3, and 2.0 mg/kg for FR and 0.1, 0.3, and 1.0 mg/kg for PR) was assessed. In a separate group of mice trained on a three-choice visual discrimination task, the task was reversed (light+, dark+, light+, dark+) 3 times to determine acquisition and reversal of the visual discrimination rule. Scopolamine hydrobromide was examined in this paradigm with the reversal task, and was used to determine learning acquisition and rule reversal learning. RESULTS: Mice rapidly acquired the FR and PR schedules, as well as both three-choice visual discrimination procedures in the nine-hole box. d-Amphetamine significantly reduced performance on the FR5 and FR10 schedules as shown by the reduction in the number of rewarded responses and the increases in various latency measurements. As expected, d-amphetamine induced an increase in the break point and eliminated the pauses that occurred on high ratio schedules under the PR3 paradigm. Pretreatment of scopolamine decreased accuracy in the three-choice visual discrimination task. CONCLUSIONS: The nine-hole box is an effective tool to assess operant behaviours in mice following pharmacological manipulation validating the utility of this apparatus for the behavioural evaluation of drug-induced and transgenic models of neurodegenerative disorders.

Amphetamine↗