Use of an Internet-based journal club.
The on-line journal club is a useful example of the educational advantages created by the combination of current Internet technology with traditional journal club methods.
Communication↗
Biomedical subjects
M G Stewart
Publications and source records attributed to M G Stewart.
Ultrastructural synaptic correlates of spatial learning in rat hippocampus.
Memory formation is believed to alter neural circuitry at the synaptic level. Although the hippocampus is known to play an important role in spatial learning, no experimental data exist on the synaptic correlates of this process at the ultrastructural level. Here, we have employed quantitative electron microscopy in order to compare the density, size and spatial arrangement of synapses in the dentate gyrus, and in area CA1, of spatially trained (water maze, invisible platform) versus control (visible platform) rats. No training-associated changes of hippocampal volume were found using a stereological estimaion (disector) of the volume density of dentate granule, or CA1 pyramidal cells. Nor were changes found in either density, or sizes of synapses (spinous or dendritic), in CA1 or dentate gyrus. However, analysis of synaptic spatial distribution showed a training-associated increase in the frequency of shorter distances (i.e. clustering) between synaptic active zones in CA1, but not dentate, thus indicating alterations in local neural circuitry. This finding indicates subtle changes in synaptic organization in area CA1 of the hippocampus following a learning experience, suggesting that spatial memory formation in mammalian hippocampus may involve topographical changes in local circuitry without synapse formation de novo.
Animals↗
Intracranial complications of sinusitis.
Intracranial suppurative complications of sinusitis remain a challenging and contemporary topic. To determine the prevalence of sinogenic sources in intracranial infectious complications, we reviewed the records at a large public hospital between 1985 and 1995. There were 203 patients with 212 suppurative intracranial infections. Sinogenic sources were identified in 12 patients with 19 infections. Most patients had ethmoid or frontal sinusitis. We discuss the presentation, microbiology, diagnosis, treatment, and clinical course of these 12 cases. The diagnosis of intracranial complications of sinusitis requires a high index of suspicion and radiographic imaging of the head and paranasal sinuses. The mean hospital stay was 31.4 days and all 12 patients survived, although three patients had significant neurologic sequelae.
Acute Disease↗
Development of a new outcomes instrument for conductive hearing loss.
OBJECTIVE: The objective was to design and validate a disease-specific outcomes instrument for use in conductive hearing loss (CHL). STUDY DESIGN: The study was a retrospective survey of 47 patients recently treated for CHL with either a hearing aid or surgery. Patients were tested with the newly designed instrument (the Hearing Satisfaction Scale [HSS]), previously validated hearing-specific instruments, and a generic quality-of-life instrument. SETTING: The study was performed in an academic tertiary referral center. MAIN OUTCOME MEASURES: These included test-retest reliability, internal consistency reliability, content validity, criterion validity, and construct validity of the HSS. RESULTS: Test-retest reliability (r = 0.72, p < 0.001) and internal consistency reliability were adequate (Cronbach's alpha was 0.83 and 0.74 for the two subscales of the HSS). Criterion validity for individual items was adequate (r = 0.45, p = 0.02) using audiometric data as the criterion standard. Construct validity was also high using results from other instruments; both convergent and divergent validity of the HSS was demonstrated. In addition, the HSS demonstrated the ability to differentially discriminate between subgroups when grouped by level of hearing loss. CONCLUSIONS: The HSS is a valid and reliable instrument for use in outcomes research on conductive hearing loss.
Adult↗
mu-Opioid receptor binding in chicken brain in relation to degree of food restriction: a quantitative autoradiographic study.
Quantitative receptor autoradiography was used to measure differences in [3H]DAGO binding to mu-opioid receptors in selected fore- and midbrain regions of chickens subject to varying degrees of chronic food restriction: either R (a recommended restricted ration), 2R (twice recommended restricted ration) or AL (ad libitum). A significant increase in binding of 75% was observed in the paleostriatum primitivum (a homologue of the mammalian globus pallidus) with the R treatment compared to the 2R and AL treatments. This finding concurs with results of earlier pharmacological manipulations with opioid antagonists, which indicated that activation of mu-opioid receptors plays a contributory role in reinforcement of post-feeding oral stereotypies in chickens subject to the same R treatment.
Animals↗
Reduction in numerical synapse density in chick (Gallus domesticus) dorsal hippocampus following transient cerebral ischaemia.
Transient forebrain ischaemia was induced by a two-vessel occlusion method in the domestic chick. One week post-surgery, hippocampal tissue was processed for electron microscopy and synapse density assessed using the disector technique. Hippocampal volume was estimated using image analysis of serial coronal cryostat sections. The density of asymmetric synapses was significantly reduced (27%; P < 0.005) in ischaemic chicks. This appears to be a real reduction as hippocampal volume was not significantly decreased.
Animals↗
Otolaryngologic disease progression in children with human immunodeficiency virus infection.
OBJECTIVES: To evaluate the prevalence of otolaryngologic disease in children born to mothers infected with human immunodeficiency virus (HIV) and to assess the correlation between HIV disease severity and the incidence density of recurrent otitis media (OM) and sinusitis based on the revised 1994 Centers for Disease Control and Prevention (CDC) clinical-severity index. DESIGN: Case series. SETTING: Academic, tertiary care children's hospital. PATIENTS: One hundred forty-five children (73 boys, 72 girls) with vertically acquired HIV infection and 153 (77 boys, 76 girls) children who had maternal exposure to HIV but later were found not to be infected ("seroreverters"), followed up on a regular basis since birth. MAIN OUTCOME MEASURES: Prevalence of recurrent OM (3 episodes in 6 months or 4 episodes in 12 months), sinusitis, parotitis, and lymphadenopathy; incidence density of recurrent OM and sinusitis based on the 1994 CDC clinical-severity index. RESULTS: Sixty-four HIV-infected children (44%) and 13 seroreverters (8.5%) had recurrent OM (P < .001); 29 HIV-infected children (20%) and 1 seroreverter (0.6%) had sinusitis (P < .001). Eight HIV-infected patients developed tympanic membrane perforations and 25 HIV-infected children required otologic surgery. Three HIV-infected patients had parotitis. The incidence density of recurrent OM increased as HIV clinical (P = .001) and immunologic (P = .03) status worsened. In contrast, the incidence density of sinusitis did not significantly correlate with increased HIV disease severity. CONCLUSION: The prevalence of recurrent OM and sinusitis is significantly greater in HIV-infected children than in seroreverters. The incidence density of recurrent OM also significantly correlates with disease progression in HIV-infected children as measured by the 1994 CDC clinical-severity index.
Disease Progression↗
D-cycloserine causes transient enhancement of memory for a weak aversive stimulus in day-old chicks (Gallus domesticus).
The N-methyl-D-aspartate (NMDA) receptor plays an important role in acquisition of memory after one-trial passive avoidance training in day-old chicks. Here, we examined the effect of D-cycloserine, a partial agonist of the glycine site on the NMDA receptor, on memory retention after training on weak aversive stimuli (10% methyl anthranilate). Bilateral, or unilateral, intracranial injections of 5 microliters of 600 mumol.l-1 D-cycloserine (DCS) were made into the intermediate and medial hyperstriatum ventrale 5 min posttraining and chicks were tested either 30 min or 1, 6, or 24 h later. Enhanced memory retention (number of chicks avoiding) occurred after bilateral, or left hemisphere, injections of DCS (compared to saline-injected controls), when chicks were tested at 1 and 6 h, but not at 30 min or 24 h posttraining. These data suggest that activation of the glycine site on the NMDA receptor in the immediate posttraining period can transiently extend the retention period of memory for a weak aversive stimulus.
Animals↗
The involvement of dopamine in the striatum in passive avoidance training in the chick.
Quantitative receptor autoradiography was used to investigate the distribution of binding of [3H]SCH 23390 to dopamine (D1) and [3H]spiroperone to D2 receptors in regions of the forebrain of the one-day-old domestic chick (Gallus domesticus). High levels of specific binding of the D1 and D2 ligands were found in the striatal regions (paleostriatum augmentatum and lobus parolfactorius) of the one-day-old chick, as reported previously in the pigeon, turtle and rat, whilst binding levels were considerably lower in the pallidum (paleostriatum primitivum), hippocampus and hyperstriatum ventrale. The proportions of D1 and D2 receptor binding in the chick were relatively similar in the striatum and pallidum, apart from the paleostriatum augmentatum, where D2 receptors outnumber those of D1 by a factor of two. Binding of the D1 and D2 ligands to forebrain regions was also investigated 30 min after one-trial passive avoidance training of one-day-old chicks in which the aversive stimulus was a bead coated with a bitter tasting substance, methyl anthranilate. These experiments demonstrated a large and highly significant bilateral increase (compared to control birds) in binding to D1 (but not D2) receptors in the lobus parolfactorius. In this striatal region, equivalent to the caudate-putamen of mammals, previous studies have shown that synaptic and dendritic alterations occur following avoidance training. It is concluded that alterations in dopamine binding may be involved in processes that result in modification of the pecking response in chicks after avoidance training.
Animals↗
Branching of active dendritic spines as a mechanism for controlling synaptic efficacy.
Recent experimental findings (Yuste R. and Denk W. (1995) Nature 375, 682-684) suggest that dendritic spines possess excitable membranes. Theoretically, it was shown earlier that the shape of active spines can significantly affect somatopetal synaptic signal transfer. Studies of long-term potentiation in the hippocampus have related the increased synaptic efficacy to a number of structural modifications of spines, including an increased number of branched spines [Trommald M. et al. (1990) In Neurotoxicity of Excitatory Amino Acids, pp. 163-174. Raven Press, New York] and a strengthened capability for spines to alter their spatial positions [Hosokawa T. et al. (1995) J. Neurosci. 15, 5560-5573]. In the present simulation study, the potential physiological impact of several types of spine changes was examined in a compartmental neuron model built using the neuromodelling software NEURON [Hines M. (1993) In Neural Systems: Analysis and Modeling, pp. 127-136. Kluwer Academic, Norwell, MA]. The model included 30 complex spines, with dual component synaptic currents and mechanisms of Ca2+ uptake, diffusion, binding and extrusion within spine heads. The results show that local clustering properties of spine distributions along dendrites are unlikely to affect synaptic efficacy. However, partial fusion of active spines, which results in formation of spine branches, or subtle changes in spine branch positions, could alone significantly increase synaptic signal transfer. These data illustrate possible mechanisms whereby subtle morphological changes in dendritic spines (compatible with changes reported in the literature) may be linked to the cellular mechanisms of learning and memory.
Calcium↗
Chronic rhinocerebral mucormycosis.
Rhinocerebral mucormycosis is a well-described fulminant fungal infection that typically presents acutely in patients with diabetic ketoacidosis or immunosuppression. Chronic presentations of rhinocerebral mucormycosis have also been described. In the chronic infection, the disease course is indolent and slowly progressive, often occurring over weeks to months. The authors report 2 cases of chronic rhinocerebral mucormycosis (CRM) treated at their institution and review 16 other cases reported in the English-language literature. In these cases, the median time from symptom onset to diagnosis was 7 months. The most common presenting features of CRM are ophthalmologic and include ptosis, proptosis, visual loss, and ophthalmoplegia. CRM occurs predominantly in patients with diabetes and ketoacidosis. The incidence of internal carotid artery and cavernous sinus thrombosis is higher in CRM patients than in those with the acute disease, although the overall survival rate for CRM patients is 83%. CRM is clinically distinct from chronic Entomophthorales infection.
Aged↗
Penetrating injuries of the face.
We reviewed 78 consecutive cases of penetrating facial injuries treated at Ben Taub General Hospital in Houston, Texas, between 1992 and 1994, and we analyzed injury patterns on the basis of (1) the mechanism of injury, and (2) the entry zone of the wounds. We found that gunshot wounds were more likely to require emergent airway establishment than shotgun wounds or stab wounds (p = 0.03). We noted a higher prevalence of globe injury among shotgun wounds than among gunshot wounds (p = 0.02). Nine (12%) patients had intracranial penetration of a bullet or shotgun pellet. Patients with gunshot wounds required open reduction and internal fixation of facial bone fractures more frequently than patients with shotgun wounds (p = 0.01). Thirty patients underwent arteriograms, and 10 demonstrated positive findings. Although there were only 3 deaths in our series, 29 (37%) patients overall had some complication caused by their penetrating facial trauma, including blindness in 12 patients. There was no significant difference in the prevalence of complications between gunshot, shotgun, and stab wounds (p = 0.18). With these injury patterns in mind, we describe an algorithm for evaluation and management of penetrating injuries of the face.
Adolescent↗
Reduction in numerical synapse density in chick (Gallus domesticus) dorsal hippocampus following transient cerebral ischaemia.
Transient forebrain ischaemia was induced by a two-vessel occlusion method in the domestic chick. One week post-surgery, hippocampal tissue was processed for electron microscopy and synapse density assessed using the disector technique. Hippocampal volume was estimated using image analysis of serial coronal cryostat sections. The density of asymmetric synapses was significantly reduced (27%; P < 0.005) in ischaemic chicks. This appears to be a real reduction as hippocampal volume was not significantly decreased.
Animals↗
Dendritic spines form 'collars' in hippocampal granule cells.
A quantitative study of the distribution of dendritic spines was carried out in three orders of dendritic branches of granule cells from the dentate gyrus of the rat hippocampus. Golgi-stained preparations (7-19 neurones in each of seven rats) were analysed using computerized microscopy. Identification of spines and quantification of stem-spine geometry was performed using a segmentation algorithm and a line skeleton transformation of dendritic images. Analysis of data using the statistics of point processes revealed that, in all three branch orders, the distribution of visible spines along dendrites was not evenly random, but included dense clusters of spines surrounding the dendritic stem (spine 'collars'). Three-dimensional reconstructions from serial ultrathin sections have confirmed the presence of such spine groups. We speculate the spine collars represent a functional element in which associative synaptic plasticity is fostered by the proximity of individual synapses.
Animals↗
Long-term increases in synaptic density in chick CNS after passive avoidance training are blocked by an inhibitor of protein synthesis.
Long-term increases in synaptic density (first recorded 24 h after training of chicks on a one-trial passive avoidance task, and still present 48 h post training), are found bilaterally in a part of the striatum, the lobus parolfactorius (LPO) [23,36], and are believed to reflect a trace of long-term memory formation. Such increases in synaptic density are most likely to occur by either de novo synthesis of new synaptic material, or via post-translational modification of pre-existing components. Several previous studies have shown that inhibitors of protein synthesis such as anisomycin injected just before, or after training, can prevent long-term memory formation in the chick. The present study therefore examined whether the long-term increases in synaptic density in the LPO that occur after passive avoidance training can be blocked by anisomycin. Our data show clearly that chicks injected with anisomycin 30 min pre-training were amnesic on testing 24 h later, and the bilateral increases in synaptic density (of spine and shaft synapses) seen in saline injected trained controls, were significantly reduced, demonstrating that protein synthesis de novo is involved in the post-training increase in synaptic density in the LPO.
Animals↗
Involvement of AMPA receptors in maintenance of memory for a passive avoidance task in day-old domestic chicks (Gallus domesticus).
Day-old chicks (Gallus domesticus) were trained on a one-trial passive avoidance task where the aversive stimulus was an unpleasant tasting substance, methyl anthranilate. Chicks were killed 6.5 h after training. The kinetic parameters of [3H] alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA) binding were determined using quantitative receptor autoradiography and Scatchard analyses in 15 discrete forebrain regions of trained and control (water-trained) chicks, revealing two components of binding in each. KD values showed some regional variation, but were 22.2 +/- 1.1 nmol l-1 for the high-affinity component and 685 +/- 25 nmol l-1 for the low-affinity component of binding to whole forebrain sections from control chicks. Analyses also revealed that Hill coefficients were significantly less than 1 in all regions measured. A significant decrease in KD for the low-affinity component occurred bilaterally in the intermediate and medial hyperstriatum ventrale (IMHV; left, 34.8%; right, 33.3%), a region that has previously been shown to be implicated in the processes of memory formation, following passive avoidance training. A significant decrease in KD for the high-affinity component occurred in the right palaeostriatum augmentatum (19.5%). Significant decreases in Bmax accompanied the KD alterations in both cases. Additionally, bilateral intracerebral injections (administered 4.5-5.5 h after training) into the IMHV of 500 nmol l-1 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective antagonist of non-NMDA glutamate receptors (particularly AMPA receptors), resulted in amnesia for one-trial passive avoidance training in day-old chicks tested 6.5 h after training.(ABSTRACT TRUNCATED AT 250 WORDS)
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Increases in NMDA receptor binding are specifically related to memory formation for a passive avoidance task in the chick: a quantitative autoradiographic study.
One-day-old chicks (Gallus domesticus) were trained on a one-trial passive avoidance task in which the aversive stimulus was an unpleasant lasting substance, methylanthranilate (MeA). Control birds were presented with a water (W) coated bead. Five minutes after training a group of McA-trained chicks were given a brief sub-convulsive trans-cranial electric shock, which rendered half amnesic whilst the remainder were able to show recall for the aversive stimulus. Thirty minutes after training birds were killed and quantitative receptor autoradiography was used to determine NMDA sensitive [3H]L-glutamate binding in specific regions of the forebrain of: (i) MeA-trained chicks; (ii) water-control chicks; (iii) MeA-trained electroshocked chicks showing recall; and (iv) MeA-electroshocked chicks amnesic for the aversive stimulus. Increases (805 in the left lobus parolfactorius and 67% in the left intermediate medial hyperstriatum ventrale) in NMDA sensitive [3H]L-glutamate binding occurred in electro-shocked chicks which showed recall of the aversive experience but were absent in MeA-trained chicks rendered amnesic by electro-shock. The increased binding in electroshocked MeA-trained birds which showed recall was similar to that observed previously in MeA-trained birds (without electroshock), compared to water control birds, whereas binding levels in McA-trained electroshocked amnesic birds were not different from those of water control birds. These data argue strongly in MeA-trained electroshocked amnesic birds were not different from those of water control birds. These data argue strongly that alterations in binding to glutamate receptor sub-types are specific to memory formation for the passive avoidance task.
Animals↗
Morphological changes associated with stages of memory formation in the chick following passive avoidance training.
Memory formation following learning is presumed to result from modification in the efficacy of neural circuitry, either through strengthening of pre-existing synapses, or formation of new contacts. An ideal paradigm to investigate memory formation is one-trial passive avoidance training of day-old chicks, in which the birds learn to avoid pecking a bead coated with an aversive substance, methylanthranilate. Following training, a sequence of biochemical, electro-physiological, pharmacological and morphological events takes place within two loci in the forebrain, the intermediate and medial hyperstriatum ventrale (IMHV), and part of the paleostriatal complex, the lobus parolfactorius (LPO). Our data reviewed here suggest that the initial acquisition of memory involves population changes in the fine spatial organization of synaptic vesicles and active zones in synapses in the IMHV whereas longer-term changes are more prominent in the LPO and involve, primarily, a bilateral increase in the density of synapses and dendritic spines. The short-term synaptic changes are as dynamic as the molecular changes which have hitherto been considered the preserve of short-term correlates of memory formation.
Animals↗