Intranasal immunisation of mice with a streptococcal peptide-based vaccine.
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Biomedical subjects
Publications and source records attributed to M Good.
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In three experiments, rats in a swimming pool were trained to find a submerged platform with a beacon attached to it. For some rats this beacon unambiguously identified the location of the platform; for others the beacon was made ambiguous by placement of an identical beacon in a different part of the pool. Test trials, in the absence of the platform and the beacons, revealed more persistent searching near the original location of the platform if the beacon attached to the platform had been ambiguous. These results show that learning about the location of the platform, with regard to cues that lie beyond the pool, is influenced by the extent to which an animal can find the platform by relying on other cues. The final experiment shows that this interaction between cues is influenced by an animal's prior experience.
Rats received excitotoxic lesions of different subsystems within the hippocampal system--either the hippocampus proper (cornu ammonis and dentate gyrus; hippocampal lesions) or the entorhinal cortex-subicular region (entorhinal lesions). Subsequently, their activity in an operant chamber was monitored both before and after footshock had been delivered (Experiment 1). Rats with hippocampal lesions showed enhanced activity before the delivery of footshock and reduced freezing after the delivery of shock. Rats with entorhinal lesions showed control levels of activity before the delivery of footshock and control levels of freezing after the delivery of footshock. Both types of lesion impaired spatial learning in a water maze (Experiment 2). These results suggest that the deficits arising from damage to the hippocampal system in contextual and spatial learning have different origins.
The contextual specificity of appetitive conditioned responding was examined in rats undergoing chronic intracerebroventricular infusion of 15 or 30 mM D-2-amino-5-phosphonopentanoic acid (D-AP5) or with excitotoxic hippocampal lesions. The magnitude of conditioned responding by control rats and rats infused with D-AP5 to a conditioned stimulus (CS) trained in Context A was attenuated when the same stimulus was presented in Context B. By contrast, hippocampal-lesioned rats displayed comparable levels of responding to the CS when presented in either Context A or B. Subsequent in vivo electrophysiological investigations showed that the D-AP5 concentrations were effective in blocking long-term potentiation (LTP) in the dentate gyrus. Results indicate that rats are capable of processing contextual information in the absence of N-methyl-D-aspartate (NMDA) receptor-dependent LTP and demonstrate an important dissociation between the effects of hippocampal lesions and the blockade of NMDA receptors in the hippocampus.
Threats to subject retention in a controlled clinical trial require strategies that encourage continued participation of subjects, with consideration of the effect of the strategies on the dependent variable. Methods to encourage retention must be based on sensitivity to the patient's changing condition and perspective. Primary considerations in the design and implementation of an intervention study are the acceptability of the intervention to particular patients and the compatibility of the intervention with other care activities. In addition, qualities of the research personnel and changes in patient conditions are important factors in retention of subjects. Vignettes illustrate the threats to retention and solutions used in a clinical trial. Threats to retention include the research nurse's approach and patient factors such as worries, control issues, visitors, symptoms of confusion and pain, and lack of cooperation. Retention strategies include supporting and educating research nurses, providing empathy and respect, including patients in decisions, negotiating with visitors, alleviating symptoms, and supporting a plan of care consistent with both the research protocol and the patient's recovery. While providing a similar approach to all groups, experimental researchers in a variable clinical environment must also provide some individualization and communication to retain valuable subjects who are ill.
Our objective was to determine the diagnostic value of CSF examinations in the diagnosis of neuroborreliosis in children with peripheral facial palsy (PFP). Paired serum and CSF samples from 21 children with PFP were investigated for antibody responses to Borrelia burgdorferi antigens using three different ELISA systems and one Western blot assay. Twenty of the children (95%) had detectable immunoglobin (Ig) M or IgG in the acute-phase serum, but discrepancies between serologic assays were noted in 33% for IgM and 22 to 50% for IgG. Intrathecal specific-antibody production was detected in five of the 20 seropositive children (25%). These five patients showed seroconversion in convalescent sera in at least one assay. Similar seroconversion suggesting recent infection with B. burgdorferi was observed in eight of the 10 children (80%) without intrathecal specific-antibody production, from whom convalescent serum samples could be obtained. All patients with intrathecal antibodies or seroconversion had shown lymphocytic pleocytosis in the acute phase of PFP. In the acute phase of PFP the detection of intrathecal production of antibodies to B. burgdorferi allows prompt diagnosis of neuroborreliosis. For patients with lymphocytic pleocytosis but no detectable intrathecal antibodies, analysis of convalescent serum may help to establish this diagnosis.
The aim of the study was to assess the prevalence, severity, associated factors and diagnosis of sleep disorders in general practice. Over 700 patients were investigated with a multiple choice questionnaire in 24 general practices in Switzerland. To assess sleep disorders, criterion A for insomnia according DSM-III-R was applied. The prevalence of sleep disorders was 44%, 64% of these were classified as mild, 31% as moderate and 5% as severe. 50% of the female patients complained about insomnia compared to 36% in males. Retrospectively, 74% of the patients stated having suffered from sleep disorders for more than one year (mild 76%, moderate 69%, severe 75%). 70% of patients with mild, 42% with moderate and 30% of patients with severe insomnia didn't inform their physicians about their sleep difficulties on the occasion of an earlier consultations. Patients with moderate or severe insomnia felt moderately or markedly disabled in their quality of life (71%) and work (58%). To estimate general anxiety and depressive state, self-rating scales were used (STAI, D-S). In comparison to reference values for healthy volunteers, insomniac patients had significantly higher scores on both scales, which were associated with the severity of sleep disorders, corroborating the association of sleep disorders with anxiety disorders and depressions. The physicians diagnosed in 18% of insomniacs a psychiatric disease, in 52% a psychoreactive disorder and in 26% a somatic etiology. The study shows that sleep disorders are a frequent syndrome in general practice and often not reported to the physician; therefore, the patients should routinely be questioned about sleep problems, and associated psychiatric diseases should be considered.
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Postoperative patients differ in their response to pain and opioids. It is therefore important that nurses offer other options as adjuvants to medication. Relaxation and music may reduce pain by interrupting the postoperative cycle of pain, muscle tension and sympathetic activity. This review summarizes and critiques studies on the effectiveness of relaxation and music use during postoperative pain. Relaxation and music were effective in reducing affective and observed pain in the majority of studies, but they were less often effective in reducing sensory pain or opioid intake. However, the between-study differences in surgical procedures, experimental techniques, activities during testing, measurement of pain, and amount of practice make comparisons difficult. Furthermore, within studies, the problems of inadequate sample size, lack of random assignment, no assurance of pretest equivalence, delayed post-test administration and no control for opiates at the time of testing reduces the validity of the studies' conclusions. Randomized controlled studies of the types of relaxation and music that are most helpful to postoperative patients should be explored in various contexts.
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The prognostic significance of magnetic resonance imaging (MRI) in the neonatal period was studied prospectively in 43 term infants with perinatal asphyxia. MRI was performed between 1 and 14 days after birth with a high field system (2.35 Tesla). Neurodevelopmental outcome was assessed by a standardized neurological examination and the Griffiths developmental test at a mean age of 18.9 months. The predictive value of the various MRI patterns was as follows: Severe diffuse brain injury (pattern AII+III; n = 7) and lesions of thalamus and basal ganglia (pattern C; n = 5) were strongly associated with poor outcome and greatly reduced head growth. Mild diffuse brain injury (pattern AI; n = 7), parasagittal lesions (B; n = 7), periventricular hyperintensity (D; n = 2), focal brain necrosis and hemorrhage (E; n = 3) and periventricular hypointense stripes (on T2-weighted images; F; n = 3) led in one third of the infants to minor neurological disturbances and mild developmental delay. Infants with normal MRI findings (G; n = 9) developed normally with the exception of one infant who was mildly delayed at 18 months. The results indicate that MRI examination during the first two weeks of life is of prognostic significance in term infants suffering from perinatal asphyxia. Severe hypoxic-ischemic brain lesions were associated highly significantly with poor neuro-developmental outcome, whereas infants with inconspicuous MRI developed normally.
Three experiments examined the effects of hippocampal lesions in pigeons on overshadowing, blocking, and a latent inhibition treatment (non-differential reinforced preexposure) using a simultaneous visual discrimination paradigm. The results showed that hippocampal damage did not influence overshadowing (Experiment 1) or blocking (Experiment 2) but did attenuate the retardation in conditioning associated with non-differential reinforced preexposure to to-be-discriminated stimuli (Experiment 3). Hippocampal birds also displayed impaired autoshaping (Experiments 1, 2, and 3). The correspondence between the behavioural effects of avian and mammalian hippocampal lesions is discussed, and the implications of the present pattern of results for avian hippocampal function are considered.
Three experiments investigated the role of the pigeon hippocampal formation (the hippocampus and area-parahippocampalis) in short-term memory for non-spatial and spatial information. The acquisition of delayed matching-to-sample and the short-term retention of non-spatial visual information, using a small set of sample stimuli, were unaffected by aspiration lesions of the hippocampus or the neostriatum (Experiment 1). Similarly, acquisition and short-term retention of non-spatial information using a successive, trial-unique, delayed non-matching-to-sample procedure were unaffected by hippocampal damage; the same birds had, however, displayed a profound autoshaping impairment (Experiment 2). Acquisition of a spatial delayed matching-to-sample task was unimpaired by hippocampal damage. However, lesioned animals were impaired following the introduction of retention intervals on this procedure (Experiment 3). The correspondence between the behavioural effects of hippocampal lesions in birds and mammals on short-term memory is discussed, and the implications of these results for avian hippocampal function are considered.
On the basis of MRI examinations in 88 neonates and infants with perinatal asphyxia, we defined 6 different patterns on T2-weighted images: pattern A--scattered hyperintensity of both hemispheres of the telencephalon with blurred border zones between cortex and white matter, indicating diffuse brain injury; pattern B--parasagittal hyperintensity extending into the corona radiata, corresponding to the watershed zones; pattern C--hyper- and hypointense lesions in thalamus and basal ganglia, which relate to haemorrhagic necrosis or iron deposition in these areas; pattern D--periventricular hyperintensity, mainly along the lateral ventricles, i.e. periventricular leukomalacia (PVL), originating from the matrix zone; pattern E--small multifocal lesions varying from hyper--to hypointense, interpreted as necrosis and haemorrhage; pattern F--periventricular centrifugal hypointense stripes in the centrum semiovale and deep white matter of the frontal and occipital lobes. Contrast was effectively inverted on T1-weighted images. Patterns A, B and C were found in 17%, 25% and 37% of patients, and patterns D, E and F in 19%, 17% and 35%, respectively. In 49 patients a combination of patterns was observed, but 30% of the initial images were normal. At follow-up, persistent abnormalities were seen in all children with patterns A and D, but in only 52% of those with pattern C. Myelination was retarded most often in patients with diffuse brain injury and PVL (patterns A and D).
The contextual specificity of the conditioned response (CR) and latent inhibition (LI) was examined in rats with selective hippocampal lesions. Acquisition of the CR to a novel conditioned stimulus (CS) was equally rapid in control and hippocampal rats (Experiments 1 and 2), and CS preexposure disrupted acquisition, (i.e., produced LI) to an equal extent in both groups (Experiment 2). In control subjects, however, the CR established in one context transferred incompletely to a second context (Experiment 1), and LI was attenuated when CS preexposure and conditioning occurred in different contexts (Experiment 3). This context specificity of the CR and LI was not apparent in hippocampal rats--the CR and LI transferred readily from one context to another. In addition, hippocampal rats were impaired in a spatial learning task (Experiment 2) but were unimpaired in learning a Pavlovian contextual discrimination (Experiment 3). These results suggest that a common contextual retrieval process underlies the contextual dependence of the CR and of LI and that this process is mediated by the hippocampus.
In 2 experiments we explored the effects of lateral versus medial laminar lesions of the hyperstriatum in pigeons (Columba livia); medical lesions were largely confined to the hyperstriatum accessorium, and lateral lesions to the hyperstriatum dorsale and hyperstriatum ventrale. In Experiment 1, lateral, but not medial, lesions disrupted acquisition of a simultaneous conditional discrimination; both medial and lateral lesions disrupted reversal of the discrimination. The reversal deficits of the medial and lateral groups were quantitatively similar, and both groups showed exaggerated positional responding. In Experiment 2, neither medial nor lateral lesions disrupted acquisition of a successive conditional discrimination. We conclude that lateral hyperstriatal damage does not obtain a general disruption of conditional learning; we speculate that the lateral hyperstriatum may play a critical role in configural learning.
We have analyzed the MRI findings from the brains of 33 children with congenital hemiplegia. Referral of these children to our hospital was either because of neurological problems or a history of complicated birth. According to maturation-dependent pathophysiological mechanisms we have classified the lesions into the following five groups: 1. malformations/prenatal encephalo-clastic lesions, 2. periventricular leukomalacia or atrophy, 3. diencephalic lesions, 4. subcortical and cortical lesions, and 5. normal findings. Combination of lesions was not uncommon. The neuroradiologically most prominent and most expanded lesions determined the classification to the different groups. We detected malformations/encephalo-clastic lesions (Group 1) in 5 children; one of these children also presented additional lesions of Groups 2 and 3. Six children displayed periventricular leukomalacia (Group 2), and in one child in combination with diencephalic and subcortical lesions. Ten children exhibited diencephalic lesions (Group 3), in one case combined with periventricular leukomalacia. The MRI of seven children showed subcortical/cortical lesions (Group 4), in four cases extending into diencephalic structures. Two children had a combination of evenly matched periventricular, diencephalic and subcortical/cortical lesions, where it was impossible to define a principal lesion. Three children had normal MRI findings. Significantly, 8 of 33 children had bilateral lesions although presenting with hemiplegia. The large proportion of diencephalic lesions, not described in similar CT studies, and the small number of normal MRI findings show the value of MRI in evaluation of congenital hemiplegia. The ability to correlate, to some extent, neuroradiological findings of damage to developmental stage affords the conclusion that at least a third of the children in our series with congenital hemiplegia suffered prenatal damage.
Simulators and training devices are used extensively by educators in 'high-tech' occupations, especially those requiring an understanding of complex systems and co-ordinated psychomotor skills. Because of advances in computer technology, anaesthetised patients can now be realistically simulated. This paper describes several training devices and a simulator currently being employed in the training of anaesthesia personnel at the University of Florida. This Gainesville Anesthesia Simulator (GAS) comprises a patient mannequin, anaesthesia gas machine, and a full set of normally operating monitoring instruments. The patient can spontaneously breathe, has audible heart and breath sounds, and palpable pulses. The mannequin contains a sophisticated lung model that consumes and eliminates gas according to physiological principles. Interconnected computers controlling the physical signs of the mannequin enable the presentation of a multitude of clinical signs. In addition, the anaesthesia machine, which is functionally intact, has hidden fault activators to challenge the user to correct equipment malfunctions. Concealed sensors monitor the users' actions and responses. A robust data acquisition and control system and a user-friendly scripting language for programming simulation scenarios are key features of GAS and make this system applicable for the training of both the beginning resident and the experienced practitioner. GAS enhances clinical education in anaesthesia by providing a non-threatening environment that fosters learning by doing. Exercises with the simulator are supported by sessions on a number of training devices. These present theoretical and practical interactive courses on the anaesthesia machine and on monitors. An extensive system, for example, introduces the student to the physics and clinical application of transoesophageal echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)