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Biomedical subjects

K M Harris

Publications and source records attributed to K M Harris.

At least 73 records · Page 4Linked to original sources

Systemic embolization complicating right ventricular myocardial infarction.

We describe a patient in whom multiple episodes of pulmonary and systemic embolization occurred in the setting of right ventricular infarction. The mechanism of paradoxical embolization was determined based on transesophageal echocardiographic findings that included right atrial spontaneous contrast, appendage thrombosis, patent foramen ovale with right-to-left atrial shunting, and absence of left ventricular thrombosis. Recurrent thromboembolization was prevented by percutaneous placement of a "clam-shell" occluder across the patent foramen. This clinical scenario may be more common than previously believed and is best detected with transesophageal echocardiography. Early identification of this condition can lead to prompt treatment and prevention of subsequent thromboembolic morbidity.

Aged↗

Variation in the number, location and size of synaptic vesicles provides an anatomical basis for the nonuniform probability of release at hippocampal CA1 synapses.

Synaptic vesicles, synaptic clefts and postsynaptic areas were measured in three dimensional reconstructions at representative axonal boutons in hippocampal area CA1. Both docked and non-docked vesicles were counted and measured. Small boutons on thin spines had about 2-6 docked vesicles from a pool of more than 200 vesicles. Medium-sized boutons on medium-sized mushroom-shaped dendritic spines contained about 13-16 docked vesicles from a pool of more than 450 vesicles. A large bouton synapsing with a large mushroom-shaped dendritic spine had two clusters of vesicles totaling more than 1000 vesicles. The postsynaptic density was segmented into two discrete zones under the two clusters of vesicles and 36 docked vesicles were distributed over its surfaces. Two multiple-synapse boutons contained more than 500 vesicles with 2-12 docked vesicles observed at each of the two postsynaptic densities on each bouton. This nonuniform number of docked vesicles provides an anatomical basis for the non-uniform probability of release that occurs across hippocampal synapses of different sizes. In addition, the volume of each synaptic vesicle was determined to be 0.4-5.2% of the total volume of the reconstructed synaptic clefts into which they presumably release their contents. However, since each vesicle contains more than 10 times the concentration of glutamate needed to saturate the postsynaptic receptors, these data also support the hypothesis that release a single synaptic vesicle will activate all of the postsynaptic receptors.

Animals↗

How multiple-synapse boutons could preserve input specificity during an interneuronal spread of LTP.

A model is proposed whereby the spread of long-term potentiation (LTP) between potentiated and neighboring neurons is initiated by a retrograde signal that is restricted to the synaptic clefts of the potentiated neurons. Next, a change, such as enhanced release of neurotransmitter, occurs in the presynaptic boutons that are associated with potentiated synapses. This change affects all synapses that are located on the potentiated boutons, and leads to LTP at synapses on neighboring neurons that share multiple-synapse boutons with the initially potentiated neurons. In this model, restricting the retrograde signal to the potentiated synaptic clefts ensures the axonal-input specificity of LTP, and the induction of the secondary LTP requires the same cellular mechanisms as those of induction of the primary LTP.

Animals↗

Informal care substitution: what we don't know can hurt us.

Empirical studies focusing on the relationship between formal and informal home care do little to quell the fears of policymakers that expanded access to public home care services will result in the withdrawal of informal support. A close examination of the studies designed to measure the withdrawal of informal support justifies this skepticism. Concerns about the withdrawal of informal care may hinder the introduction of more extensive home care benefits. Researchers have come some distance in trying to address this policy question. The conflicting nature of empirical findings, thus far, demonstrates that the answer depends heavily on how the question is framed, how home care is measured and over what time frame, and what sorts of analytic approaches are used to model the relationship between formal and informal community-based care. This article discusses these issues in greater detail and suggests strategies to address these problems in future research.

Aged↗

Quantal analysis and synaptic anatomy--integrating two views of hippocampal plasticity.

The excitatory synapses onto CA1 pyramidal cells have become a model system for understanding the activity-dependent changes in synapses that underlie learning and memory. Here we examine physiological and anatomical results that are relevant to understanding the mechanisms of synaptic transmission and plasticity at these synapses. Three main points are discussed. First, quantal analysis indicates a large heterogeneity of postsynaptic efficacies for different synapses on the same cell. Reconstructions from electron microscopy show that synapse size is also highly heterogeneous. Reasons for suspecting a relationship between synaptic size and efficacy are discussed. Second, physiological evidence indicates that the changes during long-term potentiation are both pre- and postsynaptic. Similarly, several lines of anatomical evidence suggest that plasticity affects the structure of both the pre- and postsynaptic elements. The detailed registration of structures across the synapse and the physical linkage between pre- and postsynaptic elements suggest a 'structural unit hypothesis' for coordinating pre- and postsynaptic modifications. Third, quantal analysis indicates that stimulation of a single axon can release multiple quanta. Anatomical evidence shows that cell pairs can be connected by multiple synapses, suggesting that multiple quanta may be released at independent sites. These results raise the possibility that one component of synaptic plasticity is mediated by changes in the number of functional synaptic sites.

Animals↗

Localization of synapses in rat cortical cultures.

Astrocyte-rich and astrocyte-poor cultures derived from embryonic rat cerebral cortex were compared to determine whether differences in the location of neuronal somas, dendrites, axons, synapses or astrocytes, relative to the bulk culture medium, could help to explain the large difference in neuronal susceptibility to glutamate toxicity between the two culture systems. The cultures were processed for electron microscopy, thin sectioned across their depths, and photomontaged. In astrocyte-rich cultures, most of the dendrites, axons and synapses were sequestered from the medium by a nearly continuous layer of astrocyte cell bodies and processes. In contrast, astrocytes did not cover the synapses or neuronal processes in astrocyte-poor cultures. In neither culture system were neuronal cell somas covered by glia. Since neuronal cell somas are freely exposed to the medium in both culture conditions, it seems unlikely that receptors on the somal membrane mediate the greater susceptibility of neurons in astrocyte-poor cultures to glutamate toxicity. The layer of astrocytes in the astrocyte-rich cultures may provide a physical buffer that could hinder diffusion of substances from the medium to the interstitium of the neuropil. This physical buffer combined with avid glutamate uptake mechanisms might allow astrocytes to maintain a sufficiently low concentration of glutamate in the local extracellular space to protect dendrites and synapses in the astrocyte-rich, but not in the astrocyte-poor cultures, from the excitotoxic effects of glutamate. The results of this study demonstrate that local sequestering of neurites and synapses by a physical buffer of astrocytes may help to explain the relative resistance of neurons cultured with astrocytes to glutamate toxicity. A similar physical sequestering by astrocytes, of sensitive regions of neurons in the brain, may help protect neurons from glutamate toxicity in vivo.

Animals↗

The effect on apparent size of simulated pulmonary nodules of using three standard CT window settings.

This study was undertaken to determine whether three commonly used combinations of CT display window settings permit accurate measurement of pulmonary nodule size during thoracic CT examination. Forty-five rounded nodules of synthetic material of approximate soft tissue density (+70 Hounsfield units; HU), varying in size from 5.8 mm to 21.4 mm, were suspended in surgical gauze (-900 HU to -950 HU) to simulate pulmonary nodules. CT images were obtained for each nodule using 10 mm and 2 mm CT collimation and the size of each nodule was measured at three window settings: (a) 'soft tissue setting': window width (WW) 400 HU, window level (WL) +20 HU; (b) 'lung setting'. WW 850 HU, WL -750 HU; (c) 'broad lung setting': WW 1350 HU, WL -550 HU. Measurements obtained using either lung setting were highly accurate irrespective of collimation while measurements obtained using soft tissue settings were inaccurate. The choice of display window settings is an important consideration when CT is used to assess the size of pulmonary nodules.

Humans↗

The computed tomographic appearances in chronic berylliosis.

Computed tomography (CT) of the thorax was performed in eight patients with chronic berylliosis. The pulmonary CT features were variable and included pulmonary nodularity, and patterns consistent with upper lobe fibrosis or diffuse interstitial fibrosis. Mediastinal or hilar lymphadenopathy was shown in three cases. CT clearly demonstrates the pattern and distribution of pulmonary and mediastinal involvement in chronic pulmonary berylliosis but the appearances are non-specific.

Adult↗

Breast masses in the augmentation mammaplasty patient: the role of ultrasound.

The detection and evaluation of breast parenchymal abnormalities in the presence of a radiodense implant are often difficult with standard techniques of physical examination and mammography. Breast lesions can be obscured on one or both views by the radiodense implant or concealed within the dense tissue at the prosthesis-breast tissue interface. We investigated the role of ultrasound as an adjunct to mammographic special views, including posterior displacement (Eklund et al.), in previously augmented patients who presented with a clinically palpable mass. The records of 125 consecutive breast augmentation patients seen by us over a 4-year period were retrospectively reviewed. Twenty-six patients presented with a palpable breast abnormality. All 26 patients underwent diagnostic mammograms and sonograms. Findings included 8 parenchymal lesions (4 cysts, 2 fibroadenomas, 1 seroma, 1 breast carcinoma), 8 implant-related irregularities (4 ruptures, 3 bulges, and 1 valve), and normal fibroglandular tissue in 10 patients. Mammography yielded a convincing diagnosis in 7 of 26 patients, whereas ultrasound characterized the abnormality in every case. Ultrasound is a useful adjunct to mammography in evaluating palpable breast abnormalities in the breast augmentation patient. It offers improved visualization of the breast tissue-prosthesis interface, and it is helpful in distinguishing breast parenchymal lesions from palpable irregularities of the implant.

Breast Diseases↗

Silicone implant rupture: detection with US.

The authors evaluated the ability of ultrasound (US) in detection of silicone implant ruptures and compared US detection with that of mammography and physical examination in 22 women with 29 sites of implant leakage. On sonograms, leaks were evident from a highly echogenic pattern of scattered and reverberating echoes with loss of detail posterior to the echogenic area. The area appears as a "snowstorm" and has a well-defined anterior margin but a poorly defined posterior margin. Twenty-five sites in 19 women were surgically confirmed. Mammograms obtained with various views and sonograms were available for comparison in 20 of 25 surgically confirmed leaks. Of all 29 leaks, 14 were detected at physical examination as palpable masses. Six of these 20 leaks were not detected with mammography. With US, only one leak was not detected. US allowed more accurate prediction of the extent of free silicone in the breast and enabled detection of silicone within axillary nodes. Recognition of the characteristic highly echogenic sonographic appearance of microglobules of free silicone in the soft tissues can improve detection of implant rupture.

Adult↗

Stereotypical changes in the pattern and duration of long-term potentiation expressed at postnatal days 11 and 15 in the rat hippocampus.

1. Extracellular recordings from hippocampal area CA1 lasting 2-8 h posttetanus were used to evaluate the duration of long-term potentiation (LTP) at two key developmental ages. 2. At day 11 LTP consistently endured for approximately 1 h before declining to baseline by 2.5 h posttetanus. The response could then be repotentiated, and in some cases, the repotentiation lasted longer than the original potentiation. 3. At day 15 two patterns of potentiation were observed. The first pattern was similar to that observed at day 11 in that the potentiation did not persist; however, it did endure for approximately 2-2.5 h before declining to baseline by 4 h posttetanus. In the second pattern the potentiation persisted indefinitely; these responses were monitored for 6-8 h posttetanus. 4. These patterns are similar to the temporal phases of LTP that have been revealed in adult rat hippocampus through pharmacological manipulations. They may reflect developmental changes during which the different cellular mechanisms underlying LTP become sequentially activated. 5. These findings are important for several reasons. First, because the different temporal phases of LTP seem to be added stepwise during development, animals of different ages could be used explicitly to elucidate the underlying cellular mechanisms of these phases in LTP. Second, because LTP is a candidate mechanism for some forms of learning and memory, these results have implications for sequential steps in the ontogeny of learning and memory. Finally, because studies of LTP have used animals of widely varying ages, including these two ages, it is important to consider whether differences in the developmental properties of LTP could influence experimental observations.

2-Amino-5-phosphonovalerate↗

Isolated atraumatic third nerve palsy: clinical features and imaging techniques.

We have reviewed 34 consecutive patients imaged for an isolated third nerve palsy over a 2-year period. With pupil sparing the third nerve palsy was most often due to ischaemic microvascular disease. The commonest cause of a third nerve palsy with pupillary involvement was a posterior communicating artery aneurysm. Clinical features such as speed of onset, pain and completeness of palsy were not reliable in the diagnosis of either the nature or the location of the cause. Pupillary involvement was however often associated with a compressive lesion. Imaging along the whole course of the nerve is recommended for adequate evaluation.

Adult↗

Occurrence and three-dimensional structure of multiple synapses between individual radiatum axons and their target pyramidal cells in hippocampal area CA1.

Recent physiological work has used quantal analysis to investigate the properties of synaptic transmission and long-term potentiation in hippocampal area CA1. These analyses have revealed changes in the strength of excitatory post-synaptic responses following long-term potentiation that could be mediated by cellular mechanisms in the presynaptic element, in the postsynaptic element, or in both elements. In these studies, either minimal stimulation, presumably involving a single presynaptic axon, or recordings from pairs of CA3 and CA1 cells have been used. Interpretation of these quantal analyses requires knowledge about whether single or multiple synapses occur between the presynaptic axon and its target CA1 pyramidal cells. Here, light and serial electron microscopy was used to begin to examine this question and a related question concerning the ultrastructure of spines on multiple-synapse boutons. Light microscopic analyses of Golgi preparations revealed that about 20% of the axons occurring in stratum radiatum come into close apposition with two to four different dendrites of a target CA1 cell. An "apposition" was defined as a point where the axons and dendrites crossed in the same focal plane and therefore were sufficiently close to allow a dendritic spine to reach the axon and possibly establish a synaptic contact. An additional 4% of the axons wound back and forth across individual dendrites, possibly forming multiple synapses closely spaced along the dendrites. Serial electron microscopy revealed that 24% of the individual axonal boutons in stratum radiatum make synapses with multiple dendritic spines arising from either the same or different dendritic segments. Two adjacent boutons of the same axon could also be found to synapse with different spines of the same dendrite. Together with the light microscopic analysis, these observations suggest that multiple synapses occur between single axons in stratum radiatum and their target CA1 cells, and that at least some of these synapses may occur at different electronic distances. If these multiple synapses have different physiological strengths, then they may obscure or smooth peaks in the frequency histograms that are used for quantal analyses. A three-dimensional analysis was done to compare the dimensions of pairs of dendritic spines synapsing with individual axonal boutons. When the pairs of spines associated with a single bouton arose from different dendrites, at least some of which were likely to have come from different cells, the differences between their volumes and the areas of the postsynaptic densities were on average 100% and ranged up to 650%.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Three-dimensional analysis of the structure and composition of CA3 branched dendritic spines and their synaptic relationships with mossy fiber boutons in the rat hippocampus.

This paper is the third in a series to quantify differences in the composition of subcellular organelles and three-dimensional structure of dendritic spines that could contribute to their specific biological properties. Proximal apical dendritic spines of the CA3 pyramidal cells receiving synaptic input from mossy fiber (MF) boutons in the adult rat hippocampus were evaluated in three sets of serial electron micrographs. These CA3 spines are unusual in that they have from 1 to 16 branches emerging from a single dendritic origin. The branched spines usually contain subcellular organelles that are rarely found in adult spines of other brain regions including ribosomes, multivesicular bodies (MVB), mitochondria, and microtubules. MVBs occur most often in the spine heads that also contain smooth endoplasmic reticulum, and ribosomes occur most often in spines that have spinules, which are small nonsynaptic protuberances emerging from the spine head. Most of the branched spines are surrounded by a single MF bouton, which establishes synapses with multiple spine heads. The postsynaptic densities (PSDs) occupy about 10-15% of the spine head membrane, a value that is consistent with spines from other brain regions, with spines of different geometries, and with immature spines. Individual MF boutons usually synapse with several different branched spines, all of which originate from the same parent dendrite. Larger branched spines and MF boutons are more likely to synapse with multiple MF boutons and spines, respectively, than smaller spines and boutons. Complete three-dimensional reconstructions of representative spines with 1, 6, or 12 heads were measured to obtain the volumes, total surface areas, and PSD surface areas. Overall, these dimensions were larger for the complete branched spines than for unbranched or branched spines in other brain regions. However, individual branches were of comparable size to the large mushroom spines in hippocampal area CA1 and in the visual cortex, though the CA3 branches were more irregular in shape. The diameters of each spine branch were measured along the cytoplasmic path from the PSD to the origin with the dendrite, and the lengths of branch segments over which the diameters remained approximately uniform were computed for subsequent use in biophysical models. No constrictions in the segments of the branched spines were thin enough to reduce charge transfer along their lengths.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗