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Biomedical subjects

P M Thompson

Publications and source records attributed to P M Thompson.

At least 73 records · Page 4Linked to original sources

Evidence for infanticide in bottlenose dolphins: an explanation for violent interactions with harbour porpoises?

Most harbour porpoises found dead on the north-east coast of Scotland show signs of attack by sympatric bottlenose dolphins, but the reason(s) for these violent interactions remain(s) unclear. Post-mortem examinations of stranded bottlenose dolphins indicate that five out of eight young calves from this same area were also killed by bottlenose dolphins. These data, together with direct observations of an aggressive interaction between an adult bottlenose dolphin and a dead bottlenose dolphin calf, provide strong evidence for infanticide in this population. The similarity in the size range of harbour porpoises and dolphin calves that showed signs of attack by bottlenose dolphins suggests that previously reported interspecific interactions could be related to this infanticidal behaviour. These findings appear to provide the first evidence of infanticide in cetaceans (whales, dolphins and porpoises). We suggest that infanticide must be considered as a factor shaping sociality in this and other species of cetaceans, and may have serious consequences for the viability of small populations.

Age Factors↗

Altered levels of the synaptosomal associated protein SNAP-25 in schizophrenia.

BACKGROUND: Identifying brain changes in schizophrenia has been a major research focus for many years. Although impressive gains have been made in neuroimaging and brain electrophysiology, molecular and cellular markers of schizophrenia have lagged. There are no consistent biochemical markers for schizophrenia pathophysiology and none that reflect treatment course. METHODS: Samples were obtained from 25 postmortem schizophrenic brains and 31 nonschizophrenic controls. These samples were processed, and the synaptosomal fraction was isolated. Ten micrograms of protein from each of these samples was solubilized in a sodium dodecylsulfate sample buffer and separated on 10% (wt/vol) polyacrylamide gels. Monoclonal antibody (SMI-81) was incubated with the blots and, using quantitative Western blotting, we measured the relative amounts of SNAP-25 in these samples. RESULTS: We report altered levels of SNAP-25 in both the inferior temporal cortex (Brodmann area 20) and prefrontal association cortex (Brodmann areas 9 and 10) in postmortem brains of patients with schizophrenia relative to nonschizophrenic controls. Normal levels of SNAP-25 are noted in schizophrenics in area 17, decreased levels in areas 10 and 20, and an elevated level in area 9. CONCLUSIONS: These data support cytoarchitectural observations that the cerebral cortex of schizophrenic patients has extensive pathology. The data presented here, along with data on other brain-specific proteins, indicate a complicated molecular adaptation to the causative factors of schizophrenia.

Aged↗

Prevalence and intensity of the ectoparasite Echinophthirius horridus on harbour seals (Phoca vitulina): effects of host age and inter-annual variability in host food availability.

The epidemiology of the sucking lice Echinophthirius horridus was studied over a 4 year period in which their harbour seal hosts experienced marked inter-annual changes in food availability. Prevalence and intensity of infection varied in relation to host age but not sex. Burdens were highest on immature seals, but both prevalence and intensity of infection were significantly higher in years when food availability was low. Observed intra-population variations in ectoparasite dynamics suggested that reported geographical differences in the prevalence of E. horridus may have resulted from methodological differences. In contrast to previous studies of other pinnipeds, lice were also absent on weaned pups, suggesting that E. horridus is transferred horizontally. No significant differences were found in the haematological parameters of infected and uninfected hosts. Nevertheless, there was a significant negative correlation between intensity of infection and several erythrocyte parameters, suggesting that high burdens of lice may compromise diving ability.

Age Factors↗

Psoas abscess following extracorporeal shock wave lithotripsy.

Different studies have reported renal effects like swelling of parenchyma, subcapsular and intracapsular haematoma and perinephric fluid collections. These effects were usually transient and by 2-3 months returned to normal. We report an early complication of extracorporeal shock wave lithotripsy (ESWL). A patient with solitary renal calculus who had ESWL developed psoas spasm and became unwell with elevation of white cell count and erythrocyte sedimentation rate. Psoas abscess extending from renal hilum to the groin was diagnosed and drained surgically.

Adult↗

Cortical variability and asymmetry in normal aging and Alzheimer's disease.

The onset of Alzheimer's disease (AD) is accompanied by a complex and distributed pattern of neuroanatomic change, difficult to distinguish clinically from dynamic alterations in normal aging. Extreme variations in the sulcal patterns of the human cortex have made it difficult to identify diffuse and focal variations in cortical structure in neurodegenerative disease. We report the first comprehensive 3D statistical analysis of deep sulcal structure in vivo, in both normal aging and dementia. High-resolution 3D T1-weighted fast SPGR (spoiled GRASS) MRI volumes were acquired from 10 patients diagnosed with AD (NINCDS-ARDRA criteria; age: 71.9 +/- 10.7 years) and 10 normal subjects matched for age (72.9 +/- 5.6 years), gender, educational level and handedness. Scans were digitally transformed into Talairach stereotaxic space. To determine specific patterns of cortical variation in dementia patients, 3D average and probabilistic maps of primary deep sulci were developed for both normal and AD groups. Major sulci (including supracallosal, cingulate, marginal, parieto-occipital, anterior and posterior calcarine sulci, and Sylvian fissures) were modeled as complex systems of 3D surfaces using a multi-resolution parametric mesh approach. Variations and asymmetries in their extents, curvature, area and surface complexity were evaluated. Three-dimensional maps of anatomic variability, structural asymmetry and local atrophy indicated severe regionally selective fiber loss in AD. A midsagittal area loss of 24.5% at the corpus callosum's posterior midbody (P < 0.025) matched increases in structural variability in corresponding temporo-parietal projection areas. Confidence limits on 3D cortical variation, visualized in 3D, exhibited severe increases in AD from 2 to 4 mm at the callosum to a peak SD of 19.6 mm at the posterior left Sylvian fissure. Normal Sylvian fissure asymmetries (right higher than left; P < 0.0005), mapped for the first time in three dimensions, were accentuated in AD (P < 0.0002), and were greater in AD than in controls (P < 0.05). Severe AD-related increases in 3D variability and asymmetry may reflect disease-related disruption of the commissural system connecting bilateral temporal and parietal cortical zones, regions known to be at risk of early metabolic dysfunction, perfusion deficits and selective neuronal loss in AD.

Aged↗

Sulcal variability in the Alzheimer's brain: correlations with cognition.

We mapped the three dimensional (3D) extents and variability of selected sulci in the Alzheimer's brain and explored the relationship between sulcal pattern and patient's cognitive performance. High-resolution MRIs of 10 patients with probable Alzheimer's disease (AD) were linearly transformed into a standard "normalized" 3D atlas (known as the Talairach coordinate system) and, on each relevant slice, contours of the left and right Sylvian fissure, anterior and posterior calcarine, callosal, parietooccipital, and cingulate sulci and the floor of the temporal horn of the lateral ventricle were traced. These landmarks were chosen because of their relative invariant location across individuals and because they demarcate functional boundaries relevant in AD. The sulcal contours were resolved into two-dimensional surfaces that cut through a brain volume. All 10 patients' sulcal surfaces were averaged to determine their mean spatial locations in the Talairach coordinate system. The 3D spatial extents of each patient's sulci were compared with their disease severity based on neuropsychological performance. The 3D sulcal variability, within the "normalized" atlas space, ranged from 4.0 mm for the left callosal sulcus to 9.1 mm for the left Sylvian fissure. Significant correlations were found among the spatial extents for the posterior floor of the right temporal horn of the lateral ventricle (r = -0.89, p < 0.001 for vertical extent) and right anterior calcarine sulcus (r = -0.75, p < 0.01 for anterior-posterior extent) with copying ability of the Rey-Osterrieth Complex Figure; the right anterior calcarine also had a significant relationship (r = -0.72, p = 0.02 for anterior-posterior extent) with performance on the Block Design subtest from the Wechsler Adult Intelligence Scale-Revised. Verbal fluency performance measured by the Controlled Oral Word Association Test was significantly related to the left cingulate (r = 0.91, p < 0.001 for anterior-posterior extent, and r = -0.82, p < 0.01 for vertical extent) and right cingulate (r = -0.72, p < or = 0.02 for vertical extent) sulci. This exploratory study is the first to evaluate the relationship between 3D sulcal variability and cognition; our preliminary findings suggest that the 3D pattern of sulci in the AD brain is related to the severity of the disease as reflected by cognitive performance. In the Talairach brain atlas, sulcal variability, within an AD population, approaches 1 cm. This large variability requires correction when functional imaging data are transformed into the Talairach atlas space to "normalize" individual morphologic differences.

Aged↗

Mapping histology to metabolism: coregistration of stained whole-brain sections to premortem PET in Alzheimer's disease.

The association between [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) counts obtained 8 h before death and neurofibrillary tangle (NFT) staining density in a patient with Alzheimer's disease (AD) was evaluated. In our patient FDG-PET counts were globally decreased with a greater focal deficit in the left medial temporal region independent of volume loss. After death, whole-brain sections derived from cryomacrotome sectioning were stained for NFTs by the Gallyas method and elastically warped into their native space enabling registration with premortem FDG-PET data. Gallyas staining density was localized to the paralimbic cortex of the basal forebrain, medial temporal, and orbital frontal regions. The poor correlation between NFT staining density and hypometabolism on FDG-PET implicates alternate mechanisms underlying the metabolic defect in AD.

Aged↗

Detection, visualization and animation of abnormal anatomic structure with a deformable probabilistic brain atlas based on random vector field transformations.

This paper describes the design, implementation and preliminary results of a technique for creating a comprehensive probabilistic atlas of the human brain based on high-dimensional vector field transformations. The goal of the atlas is to detect and quantify distributed patterns of deviation from normal anatomy, in a 3-D brain image from any given subject. The algorithm analyzes a reference population of normal scans and automatically generates color-coded probability maps of the anatomy of new subjects. Given a 3-D brain image of a new subject, the algorithm calculates a set of high-dimensional volumetric maps (with typically 384(2) x 256 x 3 approximately 10(8) degrees of freedom) elastically deforming this scan into structural correspondence with other scans, selected one by one from an anatomic image database. The family of volumetric warps thus constructed encodes statistical properties and directional biases of local anatomical variation throughout the architecture of the brain. A probability space of random transformations, based on the theory of anisotropic Gaussian random fields, is then developed to reflect the observed variability in stereotaxic space of the points whose correspondences are found by the warping algorithm. A complete system of 384(2) x 256 probability density functions is computed, yielding confidence limits in stereotaxic space for the location of every point represented in the 3-D image lattice of the new subject's brain. Color-coded probability maps are generated, densely defined throughout the anatomy of the new subject. These indicate locally the probability of each anatomic point being unusually situated, given the distributions of corresponding points in the scans of normal subjects. 3-D MRI and high-resolution cryosection volumes are analyzed from subjects with metastatic tumors and Alzheimer's disease. Gradual variations and continuous deformations of the underlying anatomy are simulated and their dynamic effects on regional probability maps are animated in video format (on the accompanying CD-ROM). Applications of the deformable probabilistic atlas include the transfer of multi-subject 3-D functional, vascular and histologic maps onto a single anatomic template, the mapping of 3-D atlases onto the scans of new subjects, and the rapid detection, quantification and mapping of local shape changes in 3-D medical images in disease and during normal or abnormal growth and development.

Anatomy, Cross-Sectional↗

Molecular scatology: the use of molecular genetic analysis to assign species, sex and individual identity to seal faeces.

Seals and commercial fisheries are potential competitors for fish and cephalopods. Research into the diet of British seal species has been based on conventional dietary analyses, but these methods often do not allow assignment of species identity to scat samples. We present a protocol for obtaining DNA from seal scat (faecal) samples which can be used in polymerase chain reactions to amplify both nuclear and mitochondrial DNA. This can provide a method of identifying the species, sex and individual identity of the seal, from a particular scat sample. Combined with conventional dietary analyses these techniques will allow us to assess sources of variation in seal diet composition. Scat samples have been collected from intertidal haul-out sites around the inner Moray Firth, north-east Scotland. We have assessed methods to extract and purify faecal DNA, a combination of DNA from the individual seal, prey items, and gut bacteria, for use in PCR. Controls using faecal and blood samples from the same individual have enabled microsatellite primer sets from four pinniped species to be tested. Approximately 200 scat samples have been examined for species identity and individual matches. This study will provide essential information for the assessment of interactions between seals and commercial or recreational fisheries.

Animals↗

Growing placebo response rate: the problem in recent therapeutic trials?

Recently the development of several promising new compounds for anxiety and depression was discontinued because of difficulty demonstrating therapeutic effects. This article explores alternatives to "increasing placebo response rate" as explanations. We reanalyzed a study of 81 panic patients treated with placebo, alprazolam 2 mg or 6 mg, or imipramine 225 mg daily to investigate the effect of baseline pathology and selective effects of treatment on biological and cognitive components of panic disorder. The regression of endpoint on baseline number of spontaneous panic attacks differed among treatment groups, with lower slopes for the more active compounds. Only patients with many panic attacks at baseline benefited from the active compounds. Also, treatment effects declined progressively on the more cognitive aspects of the disorder (situational panic attacks and phobia ratings) for alprazolam and were entirely absent for imipramine. Implications for the etiology of panic disorder, its treatment, and therapeutic research are discussed.

Alprazolam↗

Three-dimensional statistical analysis of sulcal variability in the human brain.

Morphometric variance of the human brain is qualitatively observable in surface features of the cortex. Statistical analysis of sulcal geometry will facilitate multisubject atlasing, neurosurgical studies, and multimodality brain mapping applications. This investigation describes the variability in location and geometry of five sulci surveyed in each hemisphere of six postmortem human brains placed within the Talairach stereotaxic grid. The sulci were modeled as complex internal surfaces in the brain. Heterogeneous profiles of three-dimensional (3D) variation were quantified locally within individual sulci. Whole human heads, sectioned at 50 micrometer, were digitally photographed and high-resolution 3D data volumes were reconstructed. The parieto-occipital sulcus, the anterior and posterior rami of the calcarine sulcus, the cingulate and marginal sulci, and the supracallosal sulcus were delineated manually on sagittally resampled sections. Sulcal outlines were reparameterized for surface comparisons. Statistics of 3D variation for arbitrary points on each surface were calculated locally from the standardized individual data. Additional measures of surface area, extent in three dimensions, surface curvature, and fractal dimension were used to characterize variations in sulcal geometry. Paralimbic sulci exhibited a greater degree of anterior-posterior variability than vertical variability. Occipital sulci displayed the reverse trend. Both trends were consistent with developmental growth patterns. Points on the occipital sulci displayed a profile of variability highly correlated with their 3D distance from the posterior commissure. Surface curvature was greater for the arched paralimbic sulci than for those bounding occipital gyri in each hemisphere. On the other hand, fractal dimension measures were remarkably similar for all sulci examined, and no significant hemispheric asymmetries were found for any of the selected spatial and geometric parameters. Implications of cortical morphometric variability for multisubject comparisons and brain mapping applications are discussed.

Aged↗

High-resolution random mesh algorithms for creating a probabilistic 3D surface atlas of the human brain.

Striking variations exist, across individuals, in the internal and external geometry of the brain. Such normal variations in the size, orientation, topology, and geometric complexity of cortical and subcortical structures have complicated the problem of quantifying deviations from normal anatomy and of developing standardized neuroanatomical atlases. This paper describes the design, implementation, and results of a technique for creating a three-dimensional (3D) probabilistic surface atlas of the human brain. We have developed, implemented, and tested a new 3D statistical method for assessing structural variations in a data-base of anatomic images. The algorithm enables the internal surface anatomy of new subjects to be analyzed at an extremely local level. The goal was to quantify subtle and distributed patterns of deviation from normal anatomy by automatically generating detailed probability maps of the anatomy of new subjects. Connected systems of parametric meshes were used to model the internal course of the following structures in both hemispheres: the parieto-occipital sulcus, the anterior and posterior rami of the calcarine sulcus, the cingulate and marginal sulci, and the supracallosal sulcus. These sulci penetrate sufficiently deeply into the brain to introduce an obvious topological decomposition of its volume architecture. A family of surface maps was constructed, encoding statistical properties of local anatomical variation within individual sulci. A probability space of random transformations, based on the theory of Gaussian random fields, was developed to reflect the observed variability in stereotaxic space of the connected system of anatomic surfaces. A complete system of probability density functions was computed, yielding confidence limits on surface variation. The ultimate goal of brain mapping is to provide a framework for integrating functional and anatomical data across many subjects and modalities. This task requires precise quantitative knowledge of the variations in geometry and location of intracerebral structures and critical functional interfaces. The surface mapping and probabilistic techniques presented here provide a basis for the generation of anatomical templates and expert diagnostic systems which retain quantitative information on intersubject variations in brain architecture.

Algorithms↗

The oldest reported patient with fibromuscular dysplasia of the renal artery.

An 80-year-old woman was brought to the emergency department with accelerated hypertension. Multiple medical regimens failed, including an angiotensin-converting enzyme inhibitor, which caused acute renal failure. Results of a renal scan for captopril were negative; renal arteriogram revealed fibromuscular dysplasia of the right renal artery. Percutaneous transluminal angioplasty was successful in dilating the renal artery and making blood pressure easier to control. Although more common in younger people, fibromuscular dysplasia should be considered in patients who are elderly and have hypertension that is difficult to control. Transluminal angioplasty should be attempted to preserve renal function and control blood pressure.

Aged↗

Informatics and computational neuroanatomy.

Rapid and convenient access to digital image archives, as well as archive-based computational tools, are fundamental to many hypothesis-driven investigations of brain anatomy and function in health and disease. The complexity and density of brain image data requires the design of intelligent tools which allow scientific and clinical data, collected at numerous research centers, to be compared, integrated, and disseminated. We describe our results in the development of image data navigational tools, a World Wide Web repository of image analysis software, and strategies to represent populations of brain image data involving atlas descriptions of its variance.

Algorithms↗

Polygraphic sleep measures differentiate alcoholics and stimulant abusers during short-term abstinence.

We hypothesized that stimulant abusers would sleep more and have more rapid eye movement (REM) sleep than primary alcoholics during acute withdrawal (first 10 days drug free) but would have opposite patterns during subacute withdrawal (days 11-14 drug free). We compared polygraphic sleep patterns during acute withdrawal (days 3-10) for 7 stimulant abusers and 8 alcoholics and during subacute withdrawal (days 11-14) for 7 different stimulant abusers and 8 different alcoholics. For comparison purposes, a group of normal controls from our preexisting database were matched for age and gender. Two statistically significant interactions were found: consistent with our hypothesis, stimulant abusers showed greater total sleep (TST) and REM sleep during acute withdrawal than subacute withdrawal, compared with alcoholics. In contrast, alcoholics showed less TST and REM sleep during acute withdrawal than during subacute withdrawal. Our polygraphic sleep data support the hypothesis that physiological withdrawal differs in alcoholics compared with stimulant abusers. Different mechanisms may underlie withdrawal in these two substances.

Acute Disease↗

Synthesis and characterization of fluoropolymeric substrata with immobilized minimal peptide sequences for cell adhesion studies. I.

In this work, poly(tetrafluoroethylene-co-hexafluoropropylene) (also known as fluorinated ethylene propylene; FEP) was functionalized at the surface using a radio frequency glow discharge plasma. This particular surface modification produced controlled densities of hydroxyl functionality on the FEP surface. These surface hydroxyl groups provided sites for the covalent attachment of minimal peptide sequences, that are specific for neuronal attachment. FSCA, ATR-FTIR, ToF-SIMS, and fluorescence spectroscopy were used to evaluate peptide reaction efficiencies and to verify that intact peptide sequences were covalently attached to the FEP surfaces. These modified substrata were then used to study the cell attachment and response to covalently bound minimal peptide sequences. Cell attachment and differentiation results using NG108-15 and PC12 neuronal cell lines are presented in the adjoining paper by Ranieri et al.

Amino Acid Sequence↗

Gender differences in outpatient research subjects with affective disorders: a comparison of descriptive variables.

BACKGROUND: Gender may play an important role in the etiopathophysiology of psychiatric illness and has become a subject of increasing interest because of its possible effects on biological markers, treatment outcome, and prognosis. Intrigued by this issue and as part of our attempt to further characterize research subjects in San Diego, we evaluated male and female research subjects from our affective disorders clinical research center on a variety of measures. Based on epidemiologic data, we postulated that female and male subjects would be similar to epidemiologic samples and would differ in terms of comorbid diagnoses and that female subjects would be more likely to have had a history of previous treatment. METHOD: The demographic characteristics; coffee, tobacco, and alcohol consumption patterns; symptom patterns; and current and lifetime comorbid DSM-III-R Axis I diagnoses of 124 female and 69 male outpatient research subjects were contrasted. RESULTS: Female research subjects had more comorbid problems with anxiety disorders, were more likely to have been previously treated, and were more likely to have a family history of psychiatric illness. CONCLUSION: Male and female research subjects were remarkably similar with respect to most characteristics assessed but, as postulated, differed in terms of their comorbid diagnoses and prior treatment history.

Adult↗