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PubMed2004

Tamoxifen and vitamin E treatments delay symptoms in the mouse model of Niemann-Pick C.

Niemann-Pick C disease (NPC) is an irreversible neurodegenerative disorder without current treatment. It is the result of deficient intracellular cholesterol movement. We investigated the effects of tamoxifen and vitamin E (D-alpha tocopherol) treatment on patterns of weight loss and motor function in the mouse model of Niemann-Pick C disease (Npc1-/- mice). Tamoxifen has multiple metabolic effects, including reducing oxidative damage, while vitamin E primarily has this property. Npc1-/- mice were identified and treatment was initiated at an approximate age of 21 days. Tamoxifen suspended in peanut oil was administered via intraperitoneal injection (weekly, at a dose calculated to deliver 0.023 microg/g/day). Vitamin E (25 IU) was administered orally via gavage once a week. Weight loss and Rota-Rod performance were analyzed by using Kaplan-Meyer survival curves. Tamoxifen treatment by itself significantly delayed weight loss (an endpoint of neurodegeneration) in male and female mice compared to untreated controls. Motor function was evaluated by performance on a Rota-Rod. Tamoxifen maintained Rota-Rod performance for about an extra week. Vitamin E treatment significantly delayed weight loss in females only. Rota-Rod performance was maintained slightly longer in mice treated with vitamin E. Simultaneous use of both treatments did not delay weight loss longer than tamoxifen-only treatment but had a greater effect than either treatment alone on Rota-Rod performance and demonstrated a significant positive effect on the early "learning curve" portion of the Rota-Rod evaluations. We found significant but relatively small improvements in rate of disease progression by treating Npc1-/- mice with tamoxifen and/or vitamin E. Some sex differences in response and an early improvement in Rota-Rod performance suggest areas for further study.

Animals↗

PubMed1992

Stimulation at a site of auditory-somatosensory convergence in the medial geniculate nucleus is an effective unconditioned stimulus for fear conditioning.

The medial division of the medial geniculate nucleus (MGm) and the posterior intralaminar nucleus (PIN) are necessary for fear conditioning to an auditory conditioned stimulus (CS), receive both auditory and somatosensory input, and project to the amygdala, which is involved in production of fear conditioned responses. If CS-unconditioned stimulus (US) convergence in the MGm-PIN is critical for fear conditioning, then microstimulation of this area should serve as an effective US during classical conditioning, in place of standard footshock. Guinea pigs underwent conditioning (40-60 trials) using a tone as the CS and medial geniculate complex microstimulation as the US. Conditioned bradycardia developed when the US electrodes were in the PIN. However, microstimulation was not an effective US for conditioning in other parts of the medial geniculate or for sensitization training in the PIN or elsewhere. Learning curves were similar to those found previously for footshock US. Thus, the PIN can be a locus of functional CS-US convergence for previously for footshock US. Thus, the PIN can be a locus of functional CS-US convergence for fear conditioning to acoustic stimuli.

Amygdala↗

PubMed1985

Learning and retrieval rate of words presented auditorily and visually.

Mode of presentation (visual or auditory) of a multitrial free recall test is stressed as an important factor in improving the diagnosis of certain neurological patients. For further use in neuropsychological research, an experiment was carried out using normal subjects, in which the effects of presentation mode and order of modality were investigated. There were no differential effects of these variables on several parameters, such as the number of words recalled and the learning curve. The time needed for the responses in immediate recall was the same in both auditory and visual conditions. In delayed recall, however, the interresponse times were significantly shorter when words had been presented auditorily than when presented visually. The results are discussed in light of further application in the field of neuropsychology.

Adult↗

PubMed2002

Use of contact lenses to correct aphakia in children.

BACKGROUND: Contact lenses play an important role in the management of childhood aphakia. However, the use and care of the lenses can be challenging. The aim of this study was to determine how parents coped and what problems they encountered. METHODS: Thirty-one families of aphakic children who were fitted with contact lenses between 1990 and 1997 were contacted and invited to participate in a telephone survey. RESULTS: Thirty families agreed to participate. Eighteen families (60%) were still using contact lenses successfully at the time of the study. Four families (13.3%) stopped using contact lenses within a year because of overwhelming difficulties handling the lenses. There was an initial learn-ing process that was often stressful and frustrating. The learning curve lasted from 1 to 24 months (first quartile 2.0 months; median 3.3 months; third quartile 15.0 months). The personality of the parent, temperament of the child and the frequency at which problems occurred may all have contributed to how each family coped with the lenses. Common initial problems included inserting the lenses into the eyes of an uncooperative child and the loss of lenses. Other problems included irritation associated with dryness, and the financial cost of maintaining the lenses. CONCLUSION: Although most parents initially found contact lenses daunting, 70% of families surveyed eventually learned to cope well. Parents felt that proper education of both parents and children on why the lenses were required, a good appreciation of problems that may occur, a strong social support network and adequate financial aid were important factors in learning to cope.

Adaptation, Psychological↗

PubMed2006

The impact of laparoscopic bariatric workshops on the practice patterns of surgeons.

BACKGROUND: This study was designed to evaluate the impact of a 2-day laparoscopic bariatric workshop on the practice patterns of participating surgeons. METHODS: From October 1998 to June 2002, 18 laparoscopic bariatric workshops were attended by 300 surgeons. Questionnaires were mailed to all participants. RESULTS: Responses were received from 124 surgeons (41%), among whom were 56 bariatric surgeons (open) (45%), 30 advanced laparoscopic surgeons (24%), and 38 surgeons who performed neither bariatric nor advanced laparoscopic surgery (31%). The questionnaire responses showed that 46 surgeons (37%) currently are performing laparoscopic gastric bypass (LGB), 38 (31%) are performing open gastric bypass, and 39 (32%) are not performing bariatric surgery. Since completion of the course, 46 surgeons have performed 8,893 LGBs (mean, 193 cases/surgeon). Overall, 87 of the surgeons (70%) thought that a limited preceptorship was necessary before performance of LGB, yet only 25% underwent this additional training. According to a poll, the respondents thought that, on the average, 50 cases (range, 10-150 cases) are needed for a claim of proficiency. CONCLUSION: Laparoscopic bariatric workshops are effective educational tools for surgeons wishing to adopt bariatric surgery. Open bariatric surgeons have the highest rates of adopting laparoscopic techniques and tend to participate in more adjunctive training before performing LGB. There was consensus that the learning curve is steep, and that additional training often is necessary. The authors propose a mechanism for post-residency skill acquisition for advanced laparoscopic surgery.

Bariatric Surgery↗

PubMed1996

MR staging of prostate cancer. How we can improve our accuracy with decisions aids and optimal techniques.

This article reviews the MR staging of prostate cancer. There has been considerable variability in the MR results to date. The reasons are complex and include reader experience, the learning curve, and a lack of clear definition of the diagnostic features of advanced disease. The problems associated with achieving a consistently high degree of accuracy are discussed. The author describes a new study aimed at improving radiologists accuracy and illustrates some of the findings and specific features of advanced disease that are useful.

Clinical Competence↗

PubMed1978

Autistic children: a study of learning characteristics and programming needs.

Learning-acquisition characteristics of six autistic children were studied in order to examine programming needs. Two studies were conducted. Study 1 showed that the first step of a color-cued sequencing task required four times more trials to learn than did the remaining five steps, producing a significant learning-to-learn curve. Study 2 confirmed earlier findings that extra-stimulus prompts are comparatively ineffective with autistic children when compared to within-stimulus prompts and showed extra-stimulus prompting to be effective following the use of within-stimulus prompting on a similar task.

Autistic Disorder↗

PubMed1988

Anterior lesser curve seromyotomy and posterior truncal vagotomy for chronic duodenal ulcer: the results at five years.

In one surgical unit, 241 patients have undergone anterior gastric seromyotomy and posterior truncal vagotomy for chronic duodenal ulcer. The postoperative mortality rate was 0.4 per cent. Four patients (1.6 per cent) required a drainage procedure for gastric stasis. The first 66 patients (Group A) were followed prospectively and 58 were available for assessment at 5 years. Eight patients (14 per cent) had developed a recurrent ulcer. In seven of these patients this responded to conservative treatment with H2 receptor antagonists. One patient has required Polya partial gastrectomy for recurrent ulceration. At 5 years 47 patients (81 per cent) were placed in the Visick I or II categories. In the next 175 patients (Group B), the ulcer recurrence rate was 3 per cent, suggesting a learning curve in mastering the procedure. We conclude that the immediate and 5-year results of the first 66 patients are at least comparable with those of highly selective vagotomy. Anterior gastric seromyotomy with posterior truncal vagotomy is an easy and rapid procedure and may be more widely applicable than highly selective vagotomy.

Adult↗

PubMed1994

Electrical stimulation of the dorsal raphe nucleus as a discriminative stimulus: generalization to (+/-)-DOI.

Electrical stimulation of the dorsal raphe nucleus of Sprague-Dawley rats was used as the cue for discrimination using a taste aversion paradigm. Rats were trained to associate saccharin drinking during electrical stimulation of the dorsal raphe nucleus with LiCl injection after the session as the aversive unconditioned stimulus. In sessions without stimulation, rats were allowed to consume saccharin and received a saline injection after the session. Suppression of saccharin consumption during electrical stimulation was learned within 12 trials. Rats trained in the reverse discrimination, i.e., sessions with no electrical stimulation paired with LiCl injection, showed a similar learning curve. Animals injected prior to the session with the hallucinogenic 5-HT2 agonist (+/-)-DOI associated DOI with electrical stimulation of the dorsal raphe nucleus. Thus, animals may be trained to discriminate electrical stimulation of the dorsal raphe nucleus. Furthermore, animals generalize from activation of 5-HT2 receptors to electrical stimulation of the dorsal raphe nucleus.

Amphetamines↗

PubMed2004

Minimally invasive total knee arthroplasty: the importance of instrumentation.

MIS TKA is in the early stages of development. There are many opponents who believe that the technique is nothing more than a cosmetic modification of the standard TKA that leads to more complications and less patient satisfaction. It is important to respect these comments and to thoroughly address them. MIS surgery should not be based on the length of the incision or the cosmetic result. The term "minimally invasive" should refer to the extent of disruption of the anatomic structures about the involved joint. In the knee, the MIS approach should not violate the extensor mechanism and should not violate the suprapatellar pouch. MIS should be a capsular approach, and as such it should produce less discomfort and a faster recovery. Modifications of the MIS technique that extend the arthrotomy into the extensor mechanism, violate the suprapatellar pouch, and evert the patella while using a limited incision are not truly minimally invasive. The MIS procedure should allow the patient to recover faster while keeping the incidence of complications at the same or lower levels as the open procedure. There will certainly be a learning curve for this operation and a smaller incision with standard TKA techniques maybe the interim step for the surgeon attempting to master the new approach. MIS TKA must be performed with accurate instruments that are coordinated with the procedure. It is not possible to perform the operation with the traditional instruments that have been made for the open operations. The older instruments do not fit into the knee joint and do not allow visualization of the joint at the same time that the cuts and balancing are performed. The visual appearance is totally different and new. The surgeon must learn a completely new image of the knee joint while continuing to apply the basic principles that have been well established. The instruments are a critical part of this new technology and are central to its success. There is no room for guessing or "eye balling" the bone cuts or the alignment and balancing. Instruments and computer-assisted technology will help advance MIS surgery in the next few years. The results of MIS TKA must be thoroughly studied and compared with the existing literature. The author has tried to advance this development ina logical fashion. The initial step was to design instruments that would allow implantation of the presently accepted knee prostheses. This step has now been completed; however, the operation is not simple and is time consuming. The next step therefore is to change the prostheses to facilitate the surgery. The femoral and tibial components are presently too large for the working incision. They are now being modified so that they can be implanted in two or more pieces. This will permit less soft tissue dissection and work better with the smaller incision. The final step will incorporate computer navigational systems. All of the present instruments are designed with attachments for the appropriate arrays to interact with these systems. Ideally, the computer image will allow precise visualization of the knee, particularly the lateral side. All new surgical approaches and devices must be introduced with the expectation to improve the surgical results. There is no doubt that the final goal of this work should be technical improvement without early clinical failures or complications.

Arthroplasty, Replacement, Knee↗

PubMed2005

Clean intermittent catheterization in genitally sensate children: patient experience and health related quality of life.

PURPOSE: Clean intermittent catheterization (CIC) has proven successful for bladder emptying in children without genital sensation with success rates of 94% to 100% in select groups. A subset of the pediatric population requires CIC for bladder dysfunction, yet has normal genital sensation. This study was designed to assess our experience with CIC in genitally sensate children and the health related (HR) quality of life (QOL) for them and their families. MATERIALS AND METHODS: A multimodality questionnaire on the usage, learning curve and degree of difficulty of CIC was developed. The PedsQLtrade mark 4.0 Generic Core Scales, a reliable, validated HRQOL survey developed for pediatric patients with chronic disease, was used to assess patient and parental QOL. Children in our practice with normal genital sensation and bladder dysfunction requiring CIC were contacted to complete these questionnaires. When possible, QOL data were collected from the patient (self-report) and one or both of the parents (parent-proxy report). RESULTS: Data for 12 males and 8 females were collected, including 30 QOL questionnaires (12 self, 18 proxy). Of the patients 80% were able to learn CIC technique in 1 clinic visit with the help of a nurse. On a 10-point scale (1-not difficult, 10-very difficult) the mean degree of difficulty for learning the CIC technique was 3.25 for males and 4.00 for females (3.55 overall). On a 10-point scale (1-uncomfortable, 10-very comfortable) mean comfort level with the CIC technique was 9.12 for females and 9.46 for males (9.33 overall). On the PedsQL 100-point scale mean QOL was 83.24 for the self-report compared to 81.78 for the parent proxy report. The QOL for normal children has previously been shown as 83 (self) to 87.61 (proxy). CONCLUSIONS: CIC was an easy technique for most sensate children to learn in 1 visit and master in a short time. Overall comfort with the technique was excellent and few problems were encountered. Their HRQOL was comparable to that of normal children.

Adolescent↗

PubMed2004

Differences in spatial learning comparing transgenic p75 knockout, New Zealand Black, C57BL/6, and Swiss Webster mice.

Four strains of mice were compared regarding their relative abilities to solve the Morris water maze test of spatial memory. Members of the New Zealand Black (NZB) strain revealed steady improvement over the 6 days of training comparable to C57BL/6 mice. The neurotrophin low affinity receptor p75 knockout mouse, in which the binding region is rendered refractory to ligand, displayed profound deficits in the acquisition of this task. Members of the Swiss Webster strain performed intermediate between the poor performance of the p75 mice and the progressively improving learning curves of the NZB and C57 mice. The present results support the notion that interference with functioning of nerve growth factor (NGF) receptors on forebrain cholingergic neurons negatively impacts the animal's ability to utilize the spatial cues necessary for successful spatial navigation. This effect on NGF receptors was more behaviorally disrupting than the influence of neocortical and hippocampal ectopias as present in the NZB mice. These results support the use of the p75 knockout mouse as a model of forebrain cholinergic neuron dysfunction. On the other hand, these results do not support the use of the NZB mouse as an animal model of human learning disability and dementia.

Animals↗

PubMed2000

[Feasibility and accuracy of the combined radioisotope and blue-dye guided sentinel lymph node biopsy in breast cancer].

Sentinel lymph node biopsy is a minimally invasive operation for staging regional lymph nodes in breast cancer. This method was introduced in the last decade. However there are some remaining questions regarding labelling, surgical technique, indications, and the pathological examination of the removed sentinel lymph nodes which have to be answered before can be introduced as the routine clinical practice. 98 patients with primary breast cancer underwent double guided (radioisotope and blue-dye) sentinel lymph node biopsy in our department during a surgical feasibility study between December 1997 and February 2000. The operation was successful in 92 patients (94%). False negative rate, sensitivity and accuracy were 15%, 85% and 95% retrospectively. During the learning curve the success rate improved from 83% to 99%, the sensitivity from 79% to 89% and the accuracy from 88% to 97% and the false negative rate decreased from 21% to 11%. In T1 tumors the false negative rate and accuracy were 6% and 98%, while in T2 tumors these were 24% and 86%. Application of a larger particle sized colloid (200-600 nm), subareolar injection and next day operation technique had no effects on the results. Double guided sentinel lymph node biopsy is a sensitive surgical staging procedure which accurately predicts the lymph node status in T1 breast tumors. The technique used by us is easy to reproduce, and learn and is beneficial in technical and radiation protection aspects.

Adult↗

PubMed1993

Answering the connectionist challenge: a symbolic model of learning the past tenses of English verbs.

Supporters of eliminative connectionism have argued for a pattern association-based explanation of language learning and language processing. They deny that explicit rules and symbolic representations play any role in language processing and cognition in general. Their argument is based to a large extent on two artificial neural network (ANN) models that are claimed to be able to learn the past tenses of English verbs (Rumelhart & McClelland, 1986, Parallel distributed processing, Vol. 2, Cambridge, MA: MIT Press; MacWhinney & Leinbach, 1991, Cognition, 40, 121-157). In this article we critically review Rumelhart and McClelland's as well as MacWhinney and Leinbach's ANN models and conclude that they do not succeed in the assigned task of learning the past tenses of English verbs. In order to answer their challenge to the symbolic processing approach, we present our symbolic pattern associator (SPA)-a general-purpose pattern associator that can learn to associate arbitrary discrete patterns. We carried out several experiments with the SPA using the same set of verbs that was used in MacWhinney and Leinbach's simulation with more realistic training and testing procedures. The SPA outperformed the connectionist models by a wide margin in the accuracy of learning, and successful inductive generalizations to unseen verbs. Our SPA has very natural and psychologically realistic explanations to many psychological effects such as U-shaped learning curve, and is much closer to human subjects in predicting past tense of the pseudo-verbs. In contrast to ANNs, whose internal representations are entirely opaque, the SPA can represent the acquired knowledge in the form of production rules that allow for further higher-level processing and integration, resulting in linguistically realistic associative templates for irregular verbs and production rules for regular verbs. In the light of these findings, we conclude that eliminative connectionists' vision of cognition as simple pattern association and pattern recognition without symbolic representation is inadequate. Pattern association as such does not imply rule-less or cue-based models of language acquisition or of human learning in general.

Cognition↗

PubMed1994

Psychomotor performance during a 28 day head-down tilt with and without lower body negative pressure.

Several factors may affect psychomotor performance in space: sensory-motor changes, sleep disturbances, psychological modifications induced by the social isolation and confinement. However, psychomotor performance is difficult to assess. A battery of standardized and computerized tests, so-called "Automated Portable Test System" (APTS) was devised to ascertain the cognitive, perceptive and motor abilities and their possible fluctuations according to environmental effects. Antiorthostatic bedrest, often used to simulate weightlessness, (particularly cardiovascular modifications) also constitutes a situation of social confinement and isolation. During two bedrest experiments (with head-down tilt of -6 degrees) of 28 days each, we intended to assess psychomotor performance of 6 males so as to determine whether: on the one hand, it could be altered by remaining in decubitus; on the other, the Lower Body Negative Pressure sessions, designed to prevent orthostatic intolerance back on Earth, could improve the performance. To accomplish this, part of the APTS tests as well as an automated perceptive attention test were performed. No downgrading of psychomotor performance was observed. On the contrary, the tasks were more accurately performed over time. In order to assess the experimental conditions on the acquisition phase, the learning curves were modelled. A beneficial effect of the LBNP sessions on simple tests involving the visual-motor coordination and attention faculties can only be regarded as a mere trend. Methods used in this experiment are also discussed.

Adult↗

PubMed1998

Complications of phonosurgery: results of a national survey.

OBJECTIVE: Medialization laryngoplasty (ML) and arytenoid adduction (AA) have become common treatments for vocal fold paralysis. The widespread use of these procedures has required many surgeons to learn these new surgeries through postgraduate education sources. Little is known regarding the efficacy of the learning methods and the types and incidence of complications in a large number of surgeons' experience. METHOD: A survey consisting of 23 questions regarding complications of ML and AA was sent to 7364 otolaryngologists. RESULTS: A 33% response rate resulted in 2436 returned surveys of which 43% stated they performed ML and/or AA (n = 1039). The survey represents 14,621 cases of ML. The average respondent performed 12 ML in the past 5 years. Forty-two percent of the respondents reported experience with one or more major complication. Airway complications requiring intervention occurred more frequently following AA than ML. The most common major complications were implant migration and failure to improve voice quality. The ML revision rate was 5.4% and the reported voice quality following revision was positive in 90% of cases. A statistically significant difference in major ML complication rate was found between surgeons with experience doing fewer than 10 MLs and those with experience doing more than 10 MLs. Similar findings showed that a higher major complication rate occurred for surgeons performing fewer than two MLs per year compared with counterparts who average two or more MLs per year. A near 1% implant extrusion rate was found. Most of the extrusions occurred into the airway. CONCLUSIONS: This is a study of the use and complications of ML/AA based on more than 14,000 procedures. Wide-spread use of ML for vocal fold paralysis was found. A notable rate of poor voice quality following ML/AA was identified and led to a 5.5% revision rate for ML. Revision ML resulted in an improved voice quality in more than 90% of the reported cases. There appears to be a "learning curve" for performing ML as well as an increased complication rate for those surgeons who perform fewer than two MLs per year and have a total career experience of fewer than 10 procedures. These findings suggest that ML may result in increased complications if the surgeon is not experienced or does not perform the surgery regularly.

Arytenoid Cartilage↗

PubMed2005

Bimanual adaptation: internal representations of bimanual rhythmic movements.

From tying your shoes and clipping your tie to the claps at the end of a fine seminar, bimanual coordination plays a major role in our daily activities. An important phenomenon in bimanual coordination is the predisposition toward mirror symmetry in the performance of bimanual rhythmic movements. Although learning and adaptation in bimanual coordination are phenomena that have been observed, they have not been studied in the context of adaptive control and internal representations-approaches that were successfully employed in the arena of reaching movements and adaptation to force perturbations. In this paper we examine the dynamics of the learning mechanisms involved when subjects are trained to perform a bimanual non-harmonic polyrhythm in a bimanual index finger tapping task. Subjects are trained in this task implicitly, using altered visual feedback, while their performance is continuously monitored throughout the experiment. Our experimental results indicate the existence of significant (p<<0.01) learning curves (i.e., error plots with significantly negative slopes) during training and aftereffects with a washout period after the visual feedback ceases to be altered. These results confirm the formation of internal representations in bimanual motor control. We present a simple, physiologically plausible, neural model that combines feedback and adaptation in the control process and which is able to reproduce key phenomena of bimanual coordination and adaptation.

Adaptation, Physiological↗

PubMed2002

Genetic determinants of adult hippocampal neurogenesis correlate with acquisition, but not probe trial performance, in the water maze task.

A number of reports have indicated that adult neurogenesis might be involved in hippocampal function. While increases in adult neurogenesis are paralleled by improvements on learning tasks and learning itself can promote the survival of newly generated neurons in the hippocampus, a causal link between learning processes and adult hippocampal neurogenesis is difficult to prove. Here, we addressed the related question of whether the baseline level of adult neurogenesis is predictive of performance on the water maze task as a test of hippocampal function. We used ten strains of recombinant inbred mice, based on C57BL/6, which are good learners and show high baseline levels of neurogenesis, and DBA/2, which are known to be poor learners and which exhibit low levels of adult neurogenesis. Two of these strains, BXD-2 and BXD-8, showed a 26-fold difference in the number of newly generated neurons per hippocampus. Over all strains, including the parental strains, there was a significant correlation between the number of new neurons generated in the dentate gyrus and parameters describing the acquisition of the water maze task (slope of the learning curves). Similar results were seen when the parental strains were not included in the analysis. There was no correlation between adult hippocampal neurogenesis and probe trial performance, performance on the rotarod, overall locomotor activity, and baseline serum corticosterone levels. This result supports the hypothesis that adult neurogenesis is involved in specific aspects of hippocampal function, particularly the acquisition of new information.

Animals↗