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PubMed1994

Food aversion conditioned in anesthetized sheep.

We discovered that a food aversion could be conditioned in anesthetized sheep. Sheep were allowed to eat a familiar food (alfalfa-grain pellets) for 30 min, and 90 min later they were given either an intraruminal (IR) injection of water (C), an IR injection of LiCl (L), anesthesia followed by an IR injection of water (A), or anesthesia followed by an IR injection of LiCl (A+L). Induction of anesthesia was by an intravenous injection of pentobarbitone sodium, and maintenance of deep anesthesia was by halothane. Sheep were maintained in deep anesthesia for 2 h to ensure that the effects of LiCl on the acquisition of a food aversion, which occur within about 1 h, were completed before they awakened. When tested 5 days later, sheep that received LiCl (treatments L and A+L) consumed less alfalfa-grain pellets than sheep that did not receive LiCl (treatments C and A) (241 g vs. 306 g; p = 0.057). Intake of sheep that were anesthetized (treatments A and A+L) did not differ from that of sheep that were not anesthetized (treatments C and L) (295 g vs. 252 g; p = 0.183). Nor was there an interaction between LiCl and anesthesia (p = 0.423). Thus, we conclude that changes in preferences for foods caused by postingestive feedback occur automatically every time food is ingested (i.e., they are noncognitive), and the kind and amount of feedback is a function of the match between the food's chemical characteristics and its ability to meet the animal's current demands for nutrients.

Anesthesia, General↗

PubMed1975

Auditory localization: role of auditory pathways in brain stem of the cat.

Cats were trained to localize sound in space. The animals' localization accuracy was determined before and after one of the following operations: 1) transection of the trapezoid body, 2) unilateral and 3) bilateral transection of the lateral lemniscus, 4) unilateral and 5) bilateral transection of the brachium of the inferior colliculus. The results after bilateral transections of the lateral lemniscus and the one deep bilateral transection of the brachium of the inferior colliculus indicate that some portion of the ascending auditory system must be intact above the medulla for an animal to be able to localize sound. A small loss in accuracy of localization was found after unilateral transection of the lateral lemniscus or brachium of the inferior colliculus. This loss, when compared with the much larger loss that monaural animals show, is an indication that binaural analysis, important for sound localization, occurs at the level of the medulla. Some transections of the trapezoid body resulted in a deficit in localization ability that appeared to be complete and permanent. The position of the lesions in the trapezoid body indicated that important encoding of the binaural cues to localization most likely occurs at the superior olivary complex, probably at the medial superior olive. But the trapezoid body or other commissures of the brain stem auditory system are probably also involved in transmission of information necessary for localization to higher centers.

Animals↗

PubMed2005

Further dissociating the processes involved in recognition memory: an FMRI study.

Based on an event-related potential study by Rugg et al. [Dissociation of the neural correlates of implicit and explicit memory. Nature, 392, 595-598, 1998], we attempted to isolate the hemodynamic correlates of recollection, familiarity, and implicit memory within a single verbal recognition memory task using event-related fMRI. Words were randomly cued for either deep or shallow processing, and then intermixed with new words for yes/no recognition. The number of studied words was such that, whereas most were recognized ("hits"), an appreciable number of shallow-studied words were not ("misses"). Comparison of deep hits versus shallow hits at test revealed activations in regions including the left inferior parietal gyrus. Comparison of shallow hits versus shallow misses revealed activations in regions including the bilateral intraparietal sulci, the left posterior middle frontal gyrus, and the left frontopolar cortex. Comparison of hits versus correct rejections revealed a relative deactivation in an anterior left medial-temporal region (most likely the perirhinal cortex). Comparison of shallow misses versus correct rejections did not reveal response decreases in any regions expected on the basis of previous imaging studies of priming. Given these and previous data, we associate the left inferior parietal activation with recollection, the left anterior medial-temporal deactivation with familiarity, and the intraparietal and prefrontal responses with target detection. The absence of differences between shallow misses and correct rejections means that the hemodynamic correlates of implicit memory remain unclear.

Adolescent↗

PubMed2006

Involuntary awareness and implicit priming: role of retrieval context.

This study examined the role of retrieval context in implicit priming by manipulating percentage of word-stem index as shallow and deep processing while performing a word-stem completion task. 80 subjects were randomly divided into four groups each of 20 subjects: shallow processing or deep processing with few retrieval indices, and shallow processing or deep processing with many retrieval indices. Analysis indicated that proportion of word-stem completion was significantly higher for studied words than for nonstudied words in all four groups and that the subjects in the groups with many retrieval indices had a significantly increased proportion of word-stem completion between studied and nonstudied words than those in the groups with few retrieval indices. Postquestionnaire analysis indicated that more previously studied items were retrieved if many studied items were available during implicit word-stem completion and that only a small proportion of word-stem completion was finished with studied words by the subjects who were aware of the prior studied and test word relations in all four groups. It was concluded that having more studied words retrievable contributed to more being retrieved and that involuntary awareness had very limited influence on the priming in the implicit word-stem completion.

Adolescent↗

PubMed2001

Effects of bilateral subthalamic stimulation on cognitive function in Parkinson disease.

BACKGROUND: Chronic bilateral subthalamic deep brain stimulation (STN-DBS) is known to improve motor function in patients with Parkinson disease (PD). However, the possible effects of STN-DBS on neuropsychological functions have been studied less. OBJECTIVE: To investigate the effects of STN-DBS on neuropsychological functions in PD. DESIGN: Before-after trial. PATIENTS AND METHODS: Fifteen consecutive patients were assessed before and 3 months after implantation of stimulators for STN-DBS (postsurgical assessment with the stimulators switched on). Both assessments were performed with patients in a drug-free condition. The neuropsychological battery consisted of tests measuring memory and visuospatial and frontal functions. RESULTS: The comparison between presurgical and postsurgical performance showed a moderate deterioration in verbal memory and prefrontal and visuospatial functions, and a moderate improvement in a prefrontal task and obsessive-compulsive traits. The motor state improved in all patients. CONCLUSION: Therapy with STN-DBS improves motor symptoms in PD without any clinically relevant neuropsychological deterioration.

Aged↗

PubMed2000

Mechanisms underlying LTP of inhibitory synaptic transmission in the deep cerebellar nuclei.

Whole-cell recordings were used to investigate long-term potentiation of inhibitory synaptic currents (IPSCs) in neurons of deep cerebellar nuclei (DCN) in slices. IPSCs were evoked by electrical stimulation of the white matter surrounding the DCN in the presence of non-N-methyl-D-aspartate (non-NMDA) glutamate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (20 microM). High-frequency stimulation induced a long-term potentation (LTP) of the IPSC amplitude without changing its reversal potential, rise time, and decay-time constant. This LTP did not require the activation of postsynaptic gamma-aminobutyric acid-A (GABA(A)) receptors but depended on the activation of NMDA receptors. LTP of IPSCs in DCN neurons could also be induced by voltage-depolarizing pulses in postsynaptic neurons and appeared to depend on an increase in intracellular calcium as the LTP was blocked when the cells were loaded with a calcium chelator, 1,2-bis-(2-amino-phenoxy)-N,N,N', N'-tetraacetic acid (BAPTA, 10 mM). LTP of IPSCs was accompanied by an increase in the frequency of spontaneous IPSCs and miniature IPSCs (recorded in the presence of tetrodotoxin 1 microM), but there was no significant change in their amplitude. In addition, during the LTP, the amplitude of response to exogenously applied GABA(A) receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride was increased. Intracellular application of tetanus toxin, a powerful blocker of exocytosis, in DCN neuron prevented the induction of LTP of IPSCs. Our results suggest that the induction of LTP of IPSCs in the DCN neurons likely involves a postsynaptic locus. Plasticity of inhibitory synaptic transmission in DCN neurons may play a crucial role in cerebellar control of motor coordination and learning.

2-Amino-5-phosphonovalerate↗

PubMed1996

Laparoscopic colposuspension for total vaginal prolapse.

OBJECTIVE: To present and evaluate a new technique of modified translaparoscopic colpopexy for total vaginal prolapse following hysterectomy as an alternative surgical mode of therapy to abdominal sacral suspension or transvaginal sacrospinous ligament vaginal vault suspension. A modest modification (Group II) of this author's initial surgical technique (Group I) and postoperative observations from 1989 to 1996 are presented. METHODS: Twenty-seven patients with iatrogenic total vaginal prolapse subsequent to hysterectomy enrolled in this clinical study, which was conducted from September 1989 through February 1996. Posteriorly, vaginal apex was suspended to the deep layer of the uterosacral ligaments. The latero-posteriors vaginal cuff was suspended to the cardinal ligaments. Anteriorly, the vaginal vault was approximated to the pubocervical fascia. These procedures were performed in both groups retroperitoneally. Additionally, and only in Group II, retrpubically, at the mid-pelvic level, the pubocervical fascia and lateral superior vaginal sulci were suspended to the tendinous arch and to the fascia covering the muscles of the pelvic sidewall. This additional part of the operation constituted a modification of the initial translaparoscopic colpopexy (Group I). RESULTS: In Group I, fifteen patients had good outcome of the operation. However, patient number 16 had a recurrent total vaginal vault prolapse within 6 months following the initial laparoscopic colpopexy. Preceding an initial laparoscopic colpopexy, sacrospinous ligament suspension was performed as one of multiple corrective surgeries. This patient was subjected to the modified laparoscopic colpopexy and has been observed for over three years. The vaginal vault remains well suspended in this particular case as well as in all remaining patients in Group II. There were neither intraoperative, immediate, nor delayed postoperative complications in all 27 patients, in both groups. CONCLUSIONS: (1) When Group I results are compared with Group II results, the new, modified translaparoscopic retroperitoneal-retropubic colpopexy appeared to be a superior technique and very promising, and offers: (a) vaginal cuff suspension by using natural neighbouring genital pelvic structures, (b) reconstruction of pelvic gross/functional anatomy, placement of the vagina adequately in midline position, and alignment of the vagina parallel to the rectum, and re-constitution of proper relationship between the newly suspended vagina and pelvic viscera. (2) It is a safe operation, simple to learn, and easy to execute; however, retroperitoneal-retropubic-mid-pelvis surgical experience as well as advanced operative laparoscopic skill is needed to meet technical demands of the operation.

Adult↗

PubMed1993

Chronic pain increases brainstem proneurotensin/neuromedin-N mRNA expression: a hybridization-histochemical and immunohistochemical study using three different rat models for chronic nociception.

The role of neurotensin in the central nervous system is poorly understood. Exogenous neurotensin has potent antinociceptive effects when injected into the midbrain periaqueductal gray (PAG). Although it is present in terminals, fibers and perikarya within the PAG and other midbrain regions known for their antinociceptive circuits, it is not known whether endogenous neurotensin modulates nociception. We examined the midbrain in three different rat models for nociception to learn whether acute or chronic pain altered neuronal levels of the proneurotensin/neuromedin N mRNA (neurotensin mRNA). The models were: adjuvant-induced polyarthritis, adjuvant-induced unilateral paw inflammation, and unilateral peripheral mononeuropathy caused by ligation of the sciatic nerve. Behavioral observations confirmed that the expected symptoms developed as previously described. Within each of the three experimental models, we performed in situ hybridization histochemistry on coronal sections from three midbrain levels that included the rostral one-third of the PAG, the middle one-third of the PAG, and the caudal one-third of the PAG. At the level of the rostral PAG, we found that neither chronic nor acute nociception altered the frequencies or distributions of neurons containing neurotensin mRNA. In contrast, at the levels of the mid- and caudal one third of the PAG, the early effects of the nociceptive lesions differed from the chronic effects. During the acute phase of each model, increases in either the frequency or field area of neurons that were hybridization-positive for neurotensin mRNA were confined to the ventromedial PAG and the dorsal raphe nucleus. As the nociceptive stimuli became chronic, the early increases in neurotensin mRNA-containing neurons at the level of the middle third of the ventral PAG were diminished but remained above control levels, while increases in neurotensin mRNA began to occur in the midbrain tegmentum lateral to the PAG. The most striking increases in neurotensin mRNA expression were observed 16-17 days after the onset of nociceptive stimuli. At the level of the mid-PAG and caudal PAG, increased hybridization signal intensities and neuron frequencies occurred within the nucleus cuneiformis and the lateral tegmental nuclei, including the pedunculopontine and microcellular tegmental nuclei, as well as the deep mesencephalic nuclei. Hybridization-positive neurons in the tegmental nuclei were not observed at early stages of lesion development, but were a consistent feature of caudal midbrains after nociception became chronic.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2002

Mentoring for a new era.

OBJECTIVE: Over the course of their education, medical students must develop an identity that involves a deep understanding of professional principles and the skills to apply these ideals. This task is so important that it cannot be left to informal means and should be cultivated by a structured system that is focused on professionalism. The overall goal of our student-mentoring program is to advance the professional development of our students during the first two years of medical school through regular group meetings with skilled, trained faculty facilitators. DESCRIPTION: We shaped the program to foster meaningful mentoring relationships among students and faculty, facilitate personal reflection, and encourage exploration of larger questions related to professional development. This program has evolved from a model of individual student-faculty pairings that resulted in uneven experiences. It is organized through a new "Master Scholars Program" (MSP), inaugurated in 2001-2002. The MSP features five theme-based societies composed of students and faculty who share interests in the theme (e.g., bioethics/human rights, health policy/public health, arts/humanities in medicine, biomedical/health sciences, medical informatics/biotechnology). Approximately once per month, eight students and two faculty members from each society meet over lunch for student-led discussions on topics related to their own professional development. In the first session, structured exercises enable students to get to know one another and brainstorm a curriculum for the year. In subsequent sessions, student pairs lead discussions on topics of interest to the group ranging from "the role of medical professionals in the aftermath of the World Trade Center attacks" to "balancing careers in medicine with family." A list of each group's discussion topics is posted on an electronic bulletin board to inform others. Two faculty mentors lead each group to ensure continuity and diversity over the two-year course of their meetings. A total of 57 out of 78 (73%) attended workshops to learn about the program and enhance their facilitation skills. Professional behaviors are explicitly emphasized in the materials outlining expectations of both students and faculty. Students are expected to attend, participate in and lead discussions, be constructive, respectful, and supportive, and accept/act on constructive feedback. Mentors are to facilitate the group's process, and provide feedback and guidance about the students' ideas and passions and the challenges they encounter. The faculty mentors will contribute descriptive material for the dean's letter on each student. We assessed student understanding of the definition of professionalism prior to the mentoring program and will follow up at regular intervals. Formative evaluation of the program includes surveys and focus groups with students and faculty to assess the effectiveness of the group process in accomplishing the stated goals of the program. DISCUSSION: Our medical school has committed resources, and our faculty and students have given thought, energy, and enthusiasm, to our mentoring program. This innovative new model has the potential to deepen and enrich the culture of medicine by providing a forum and skills for students to reflect on their own professional development and interact in a meaningful way with committed and skilled faculty who share similar interests.

Education, Medical, Undergraduate↗

PubMed2003

Semantic and cross-case identity priming in patients with Parkinson's disease.

Semantic and cross-case identity priming were investigated in nondemented patients with Parkinson's disease (PD) and controls using the Lexical Decision Task. Three conditions were administered that consisted of the presentation of prime and target word pairs. In the semantic priming condition the word pairs were semantically related (e.g., table-CHAIR), in the cross-case identity priming condition the word pairs consisted of the same word (e.g., noise-NOISE), and in the unrelated condition the word pairs were not related semantically (e.g., guns-DEEP). A fourth condition was also administered that consisted of the presentation of a prime word and a pronounceable nonword target (e.g., starved-FORVE). Participants were asked to indicate whether the target was a real word or a nonword. The prime and target were separated by either a short or long (250 ms or 1000 ms) stimulus onset asynchrony (SOA). Results indicated that PD patients displayed normal semantic priming (i.e., faster responding to the target in the semantic condition as compared to the unrelated condition) at both the short and long SOA. Similarly, PD patients displayed normal cross-case identity priming (i.e., faster responding to the target in the identity condition relative to the unrelated condition) at the long SOA. At the short SOA, however, PD patients displayed hyper identity priming relative to controls (134 ms vs. 50 ms). These results suggest that semantic processes are normal in nondemented PD patients but that the processes involved in accessing lexical information may be overly activated in these patients.

Aged↗

PubMed2005

Levels-of-processing effect on frontotemporal function in schizophrenia during word encoding and recognition.

OBJECTIVE: Patients with schizophrenia improve episodic memory accuracy when given organizational strategies through levels-of-processing paradigms. This study tested if improvement is accompanied by normalized frontotemporal function. METHOD: Event-related blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) was used to measure activation during shallow (perceptual) and deep (semantic) word encoding and recognition in 14 patients with schizophrenia and 14 healthy comparison subjects. RESULTS: Despite slower and less accurate overall word classification, the patients showed normal levels-of-processing effects, with faster and more accurate recognition of deeply processed words. These effects were accompanied by left ventrolateral prefrontal activation during encoding in both groups, although the thalamus, hippocampus, and lingual gyrus were overactivated in the patients. During word recognition, the patients showed overactivation in the left frontal pole and had a less robust right prefrontal response. CONCLUSIONS: Evidence of normal levels-of-processing effects and left prefrontal activation suggests that patients with schizophrenia can form and maintain semantic representations when they are provided with organizational cues and can improve their word encoding and retrieval. Areas of overactivation suggest residual inefficiencies. Nevertheless, the effect of teaching organizational strategies on episodic memory and brain function is a worthwhile topic for future interventional studies.

Adult↗

PubMed1998

Functional-anatomic study of episodic retrieval. II. Selective averaging of event-related fMRI trials to test the retrieval success hypothesis.

In a companion paper (R. L. Buckner et al., 1998, NeuroImage 7, 151-162) we used fMRI to identify brain areas activated by episodic memory retrieval. Prefrontal areas were shown to differentiate component processes related to retrieval success and retrieval effort in block-designed paradigms. Importantly, a right anterior prefrontal area was most active during task blocks involving greatest retrieval success, consistent with an earlier PET study by M. D. Rugg et al. (1996, Brain 119, 2073-2083). However, manipulation of these variables within the context of blocked trials confounds differences related to varying levels of retrieval success with potential shifts in subjects' strategies due to changes in the probability of target events across blocks. To test more rigorously the hypothesis that certain areas are directly related to retrieval success, we adopted recently developed procedures for event-related fMRI. Fourteen subjects studied words under deep encoding and were then tested in a mixed trial paradigm where old and new words were randomly presented. This recognition testing procedure activated similar areas to the blocked trial paradigm, with all areas showing similar levels of activation across old and new items. Of critical importance, significant activation was detected in right anterior prefrontal cortex for new items when subjects correctly indicated they were new (correct rejections). These findings go against the retrieval success hypothesis as formally proposed and provide an important constraint for interpretation of this region's role in episodic retrieval. Furthermore, anterior prefrontal activation was found to occur late, relative to other brain areas, suggesting that it may be involved in retrieval verification or monitoring processes or perhaps even in anticipation of subsequent trial events (although an alternative possibility, that the late onset is mediated by a late vascular response, cannot be ruled out). These findings and their relation to the results obtained in the companion blocked-trial paradigm are discussed.

Adolescent↗

PubMed2005

Neural correlates of social odor recognition and the representation of individual distinctive social odors within entorhinal cortex and ventral subiculum.

Recognition of individual conspecifics is important for social behavior and requires the formation of memories for individually distinctive social signals. Individual recognition is often mediated by olfactory cues in mammals, especially nocturnal rodents such as golden hamsters. In hamsters, this form of recognition requires main olfactory system input to the lateral entorhinal cortex (LEnt). Here, we tested whether neurons in LEnt and the nearby ventral subiculum (VS) would show cellular correlates of this natural form of recognition memory. Two hundred ninety single neurons were recorded from both superficial (SE) and deep layers of LEnt (DE) and VS while male hamsters investigated volatile odorants from female vaginal secretions. Many neurons encoded differences between female's odors with many discriminating between odors from different individual females but not between different odor samples from the same female. Other neurons discriminated between odor samples from one female and generalized across collections from other females. LEnt and VS neurons showed enhanced or suppressed cellular activity during investigation of previously presented odors and in response to novel odors. A majority of SE neurons decreased firing to odor repetition and increased activity to novel odors. In contrast, DE neurons often showed suppressed activity in response to novel odors. Thus, neurons in LEnt and VS of male hamsters encode information that is critical for the identification and recognition of individual females by odor cues. This study reveals cellular mechanisms in LEnt and VS that may mediate a natural form of recognition memory in hamsters. These neuronal responses were similar to those observed in rats and monkeys during performance in standard recognition memory tasks. Consequently, the present data extend our understanding of the cellular basis for recognition memory and suggest that individual recognition requires similar neural mechanisms as those employed in laboratory tests of recognition memory.

Action Potentials↗

PubMed2006

Prior electrical stimulation of dorsal periaqueductal grey matter or deep layers of the superior colliculus sensitizes rats to anxiety-like behaviors in the elevated T-maze test.

Electrical stimulation of the dorsal periaqueductal grey matter (DPAG) and deep layers of the superior colliculus (DLSC) of the rat elicits anxiety-like reactions such as freezing and flight. The temporal course of the effects of the aversive electrical stimulation of the DPAG (5, 15 and 30 min afterward) and DLSC (5, 10 and 15 min afterward) on the defensive response of rats exposed to elevated T-maze were determined. The elevated T-maze generates two defensive behaviors, inhibitory avoidance and one-way escape, which have been related, respectively, to generalized anxiety and panic disorders. Prior electrical stimulation of the DPAG (15 min) and DLSC (5 min) enhanced inhibitory avoidance when compared to no-operated and sham animals, although not affecting escape. Therefore, stimulation of the DPAG and DLSC causes a heightened responsivity to anxiogenic stimulus, but not to panicogenic stimulus, inherent to elevated T-maze. These findings support the participation of the DPAG and DLSC in the elaboration of adaptive responses to stressful situations. Besides, the data supports the view that prior electrical stimulation of DPAG and DLSC is selective in sensitizing rats to anxiety-like behaviors, but not to panic-like behaviors in the elevated T-maze test.

Animals↗

PubMed2006

Texture discrimination and multi-unit recording in the rat vibrissal nerve.

BACKGROUND: Rats distinguish objects differing in surface texture by actively moving their vibrissae. In this paper we characterized some aspects of texture sensing in anesthetized rats during active touch. We analyzed the multifiber discharge from a deep vibrissal nerve when the vibrissa sweeps materials (wood, metal, acrylic, sandpaper) having different textures. We polished these surfaces with sandpaper (P1000) to obtain close degrees of roughness and we induced vibrissal movement with two-branch facial nerve stimulation. We also consider the change in pressure against the vibrissa as a way to improve the tactile information acquisition. The signals were compared with a reference signal (control)--vibrissa sweeping the air--and were analyzed with the Root Mean Square (RMS) and the Power Spectrum Density (PSD). RESULTS: We extracted the information about texture discrimination hidden in the population activity of one vibrissa innervation, using the RMS values and the PSD. The pressure level 3 produced the best differentiation for RMS values and it could represent the "optimum" vibrissal pressure for texture discrimination. The frequency analysis (PSD) provided information only at low-pressure levels and showed that the differences are not related to the roughness of the materials but could be related to other texture parameters. CONCLUSION: Our results suggest that the physical properties of different materials could be transduced by the trigeminal sensory system of rats, as are shown by amplitude and frequency changes. Likewise, varying the pressure could represent a behavioral strategy that improves the information acquisition for texture discrimination.

Action Potentials↗

PubMed2005

Psychophysics of electrical stimulation of striate cortex in macaques.

Macaques indicated their detection of onset or alteration of 0.2-ms pulses applied in various configurations through electrodes implanted in striate cortex. When microelectrodes were introduced and left in place, the threshold for detection of 100-Hz pulses nearly doubled within 24 h. However, for chronically implanted platinum-alloy macroelectrodes detection thresholds usually remained stable for many months, independently of location within striate cortex or its immediately subjacent white matter. Thresholds were unaffected by the visual conditions, such as light versus darkness, or movement of the eyes; but in one animal blind after acute glaucoma thresholds for loci in striate cortex were permanently decreased by about 50%. Learning to respond to electrical stimulation of the optic tract produced no tendency to respond to such stimulation of striate cortex. Onset of stimulation at a given locus could be detected even in the face of continuous supraliminal stimulation at four surrounding loci on a 3-mm radius. The surround stimulation did alter the threshold of the central locus, but such stimuli could not summate if they were subliminal by some 10%. Cessation of stimulation that had been continuing for 1 min to 1 h could be detected if it were being applied at a level 20-75% above that needed for detection of stimulus onset. Continuous stimulation had a pronounced "priming" effect, in that modulation of frequency or intensity of such stimulation by as little as 5% could be detected (e.g., 20 microA in a background of 500 microA, or <2-ms interpulse interval with pulses at 50 Hz). Using pulses inserted in various phase relations to ongoing pulses at 2-5 Hz, it could be determined that stimulus pulses were surrounded by a strong facilitatory period for about 30 ms, which was then replaced by refractoriness. Given the congruence of macaque and human visual anatomy and psychophysics, these results further encourage efforts to develop a cortical prosthesis for the blind.

Animals↗

PubMed1994

Ritanserin and alcohol abuse and dependence.

Ritanserin is a potent long-acting 5-HT2 antagonist that acts centrally. In humans, ritanserin increases deep slow wave sleep, improved liveliness in a variety of psychiatric disorders and facilitated participation in behaviour therapy. During clinical trials unexpected observations indicated that ritanserin may be of value in treating drug addicts. Furthermore, initial clinical observations confirmed the efficacy of ritanserin in the chronic withdrawal phase after detoxification from ethanol. In the present paper, four experiments which support the potential of ritanserin as a pharmacological treatment for alcohol abuse and dependence are described. Firstly, ritanserin has been demonstrated to lack abuse potential and any direct interaction with ethanol. Secondly, in various models ritanserin has been shown to reduce alcohol intake and preference. The level of activity varies to some degree depending on the test and treatment procedure, as well as on the animal strain used. Long term ritanserin-related efficacy was illustrated by the gradual increase in alcohol drinking after cessation of the ritanserin treatment. Thirdly, the dopaminergic pathway and the nucleus accumbens have been shown to play a role in the effects of ritanserin. Finally, ritanserin reduces some alcohol withdrawal signs. Based on these findings, a clinical development plan started. After safety-interactions studies, ritanserin was demonstrated to influence the desire to drink in normal volunteers who display heavy social drinking. Currently, three major trials in 900 alcohol-dependent patients with different levels of dependence are running.

Alcohol Drinking↗

PubMedDate not supplied

[Standards, Options and Recommendations 2000: non metastatic endometrial cancer].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Cancer Centers, and specialists from French Public Universities, General Hospitals and Private Clinics, and some specialists learned societies. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The SORs are developed using a methodology based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for the management of patients with carcinoma of the endometrium according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 63 independent reviewers. RESULTS: The main recommendations for the management of carcinoma of the endometrium are: 1) The diagnosis of carcinoma of the endometrium is based on biopsy and histological examination. However, as first intention, the first elements for diagnosis can be obtain from a hysterography, or particularly, a endovaginal ultrasound examination. Ultrasound allows locoregional metastases to be detected, the CT scan allows the lymph node involvement to be assessed and magnetic resonance imaging allows the myometrium invasion to be evaluated. 2) For the majority of patients, surgery is the initial treatment, both for localised and advanced-stage carcinomas. The excised sample can be used for pathological analysis and tumour staging, using the FIGO (Fédération internationale de gynécologie obstétrique) classification. Surgery for patients with stage I and II carcinomas involves total extrafascial hysterectomy with bilateral salpingo-oophorectomy., In patients with stage III and IV carcinomas radical surgery should be performed, when possible. If this is not possible, then surgery should be as complete as possible and be associated with a complementary treatment. In patients with the most advanced carcinomas, tumour reduction by surgery should be performed. 3) Complementary treatment includes external-beam radiotherapy and brachytherapy. The decision concerning the extent and type of irradiation should be taken taking into consideration the stage and the prognostic factors present. For patients with stage I and II carcinoma, complementary treatment with brachytherapy can be performed, if the myometrium invasion is not deep, or if the carcinoma is grade 2 or 3. Patients with stage III carcinomas can be treated with pelvic or abdominal-pelvic complementary irradiation. In patients that cannot undergo surgery, exclusive radiotherapy can be performed. 4) In the absence of any symptoms, surveillance should include a general clinical and gynaecological examination. All patients with symptoms should undergo an additional work-up.

Endometrial Neoplasms↗