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Biomedical subjects

A F Dean

Publications and source records attributed to A F Dean.

At least 19 recordsLinked to original sources
PubMed2006

Improved delineation of glioma margins and regions of infiltration with the use of diffusion tensor imaging: an image-guided biopsy study.

BACKGROUND AND PURPOSE: The efficacy of radiation therapy, the mainstay of treatment for malignant gliomas, is limited by our inability to accurately determine tumor margins. As a result, despite recent advances, the prognosis remains appalling. Because gliomas preferentially infiltrate along white matter tracks, methods that show white matter disruption should improve this delineation. In this study, results of histologic examination from samples obtained from image-guided brain biopsies were correlated with diffusion tensor images. METHODS: Twenty patients requiring image-guided biopsies for presumed gliomas were imaged preoperatively. Patients underwent image-guided biopsies with multiple biopsies taken along a single track that went into normal-appearing brain. Regions of interest were determined from the sites of the biopsies, and diffusion tensor imaging findings were compared with glioma histology. RESULTS: Using diffusion tissue signatures, it was possible to differentiate gross tumor (reduction of the anisotropic component, q > 12% from contralateral region), from tumor infiltration (increase in the isotropic component, p > 10% from contralateral region). This technique has a sensitivity of 98% and specificity of 81%. T2-weighted abnormalities failed to identify the margin in half of all specimens. CONCLUSION: Diffusion tensor imaging can better delineate the tumor margin in gliomas. Such techniques can improve the delineation of the radiation therapy target volume for gliomas and potentially can direct local therapies for tumor infiltration.

Adolescent↗
PubMed2002

Rasmussen's encephalitis followed by lupus erythematosus.

A 6-year-old female presented with right hemichorea, initially thought to be post-streptococcal, which subsequently progressed to a right dystonic hemiplegia. At 7 1/2 years she developed right focal and secondary generalized tonic-clonic seizures. These became intractable. A brain biopsy was consistent with Rasmussen's encephalitis (RE). At 9 1/2 years the child underwent a left hemispherectomy making a good recovery with resolution of seizures. At 12 years she presented with recurrent episodes of abdominal pain, fever, and malar rash with serological evidence of systemic lupus erythematosus (SLE). A possible link between RE and SLE is discussed.

Biopsy↗
PubMed2002

Measures of folding applied to the development of the human fetal brain.

Previous work has suggested the existence of differences between the cerebral cortex of normal individuals, and those of patients with diseases such as epilepsy and schizophrenia. These shape abnormalities may be of developmental origin. Improved shape measures could provide useful tools for neuroscience research and patient diagnosis. We consider the theoretically desirable properties of measures of brain shape. We have implemented seven measures, three from the neuroscience literature, and four new to this field. Three of the measures are zero-order and four are second-order with respect to the surface. We validate the measures using simple geometrical shapes, and a collection of magnetic resonance scans of ten histologically normal ex vivo fetal brains with gestational ages from 19-42 weeks. We then apply the measures to MR scans from two histologically abnormal ex vivo brains. We demonstrate that our implementation of the measures is sensitive to anatomical variability rather than to the discreteness of the image data. All the measures were sensitive to changes in shape during fetal development. Several of the measures could distinguish between the normal and abnormal fetal brains. We propose a multivariate approach to studying the shape of the cerebral cortex, in which both zero-order and second-order measures are used to quantify folding.

Aging↗
PubMed2001

Chronic encephalitis and temporal lobe epilepsy: a variant of Rasmussen's syndrome?

The authors report two adult patients with chronic temporal lobe epilepsy and pathologic features consistent with Rasmussen's encephalitis. Although seizures persisted after temporal lobe surgery no progressive cognitive or neurologic deficit has emerged. Prominent auditory auras in each suggested a persisting epileptogenic focus in the superior temporal gyrus. The current findings expand the clinical spectrum of Rasmussen's encephalitis and suggest that chronic nonprogressive encephalitis may serve as the pathologic substrate of medically intractable temporal lobe epilepsy.

Adult↗
PubMed2001

Solitary fibrous tumours of the meninges: case series and literature review.

We report four new cases of meningeal Solitary Fibrous Tumour (SFT). Two patients presented with raised intracranial pressure from posterior fossa SFT, and the third developed hemiparesis and dysphasia due to a large lesion that originated in the left middle cranial fossa. These were successfully excised and the patients remain well at follow-up of between 1 and 3 years. The fourth patient, a 71-year-old man, suffered an intracerebral haemorrhage and later died from a malignant SFT that had invaded the falx cerebri, superior sagittal sinus, and brain. This is the first description of a locally aggressive meningeal SFT with multiple atypical histological features. The 31 previously reported cases of meningeal SFT are reviewed. They occur at all ages and may be relatively more common in the posterior fossa and spine. Intracranial SFT originate from the dura and are probably indistinguishable from meningiomas on imaging and at surgery. In contrast, approximately two-thirds of spinal SFT have no dural attachment. Histologically, SFT are spindle-cell neoplasms with a characteristic immunohistochemical profile of CD34, vimentin, and bcl-2 positivity. Data on outcome for patients with meningeal SFT are limited. At other sites, however, extent of resection is the most important prognostic factor, and invasion or metastasis can occur with histologically benign SFT. Meningeal SFT should, therefore, be excised as completely as possible and followed carefully in the long-term.

Adult↗
PubMed1999

Extracellular matrix-modulated differential invasion of human meningioma cell lines in vitro.

The in vitro invasive behaviour of six meningioma cell lines of various histological sub-type and grade was assessed using Boyden chemotaxis chambers ('Transwell' units) precoated with various extracellular matrix proteins. The cell lines included a benign meningothelial (IPGS), two benign transitional (IPCBR and IPGC), one atypical (IPIH) and two malignant (IPSE and IPIR) meningiomas. IPGC was a recurrent tumour. The results showed that IPCBR was most invasive through laminin and vitronectin. IPIH was moderately invasive through collagen type IV, laminin, vitronectin and fibronectin. However, both IPSE and IPIR were less invasive than IPIH whereas, IPGS was least invasive of all. Moreover, laminin was the most permissive extracellular matrix protein for most cell lines and collagen type IV, the least permissive. These results show that there is a differential in vitro invasive behaviour of cell lines derived from different histological types of meningiomas according to extracellular matrix substrate and suggests that invasion and migration of meningiomas in situ might be modulated by various extracellular components.

Chemotaxis↗
PubMed1999

Progressive dendritic pathology in cynomolgus macaques infected with simian immunodeficiency virus.

Neuronal pathology in acquired immunodeficiency syndrome (AIDS) is of interest in relation to cognitive impairment in AIDS patients and from the broader perspective of the pathogenesis of neurodegeneration. Cortical dendritic spine loss has been described in patients with AIDS and the aim of this study was to test the hypothesis that similar pathology is present in cynomolgus macaques infected with simian immunodeficiency virus (SIV). These animals develop an AIDS-like illness, but multinucleated giant cell encephalitis is not a feature and CNS virus load is found to be very low. Four animals infected for 2.5-3 months and four infected for 2-3 years were compared with four controls. The Golgi-Cox technique was employed to demonstrate dendritic morphology in the frontal cortex and the diameter of apical dendrites, dendritic spine density and dendritic spine lengths were measured in layer V pyramidal cells. Immunohistochemistry for microtubule-associated protein-2 (MAP-2), MHC class II and glial fibrillary acidic protein (GFAP) was also performed. In infected animals there was progressive spine loss and atrophy of remaining spines with loss of MAP-2 immunoreactivity at late time points. No parallel increase in GFAP immunostaining or MHC-class II expression in microglial cells was seen. We conclude that progressive neuronal dendritic pathology is a feature of SIVmac251 infection of cynomolgus macaques and is apparent relatively early in disease. Furthermore, dendritic abnormalities occur in the absence of either multinucleated giant cell pathology or substantial CNS virus load.

Animals↗
PubMed1998

Clinicopathological study of seven cases of spinal cord teratoma: a possible germ cell origin.

AIMS: To establish the clinical and pathological aspects of teratoma affecting the spinal cord. METHOD AND RESULTS: We reviewed our neurosurgical records for the last 15 years and found seven cases of teratoma of the spinal cord. The cases were reviewed clinically, radiologically and pathologically using immunohistochemical markers to identify various tissue components. We found that spinal cord teratoma is an extremely rare tumour of spinal cord affecting patients aged 23-47 years and of approximately equal male to female distribution. The terminal portions of spinal cord and intradural location of the tumour are common. Three cases were associated with vertebral anomaly. Most tumours showed benign (mature) components derived from more than one germ cell layer; one showed malignant adenocarcinomatous component. All cases were treated by surgical resection and two recurred at 6 and 10 year intervals without malignant transformation. CONCLUSION: Spinal cord teratoma is a rare, mainly benign tumour, which could be associated with vertebral anomaly. The pathogenesis of this tumour is controversial, possibly due to germinal cell aberration.

Adenocarcinoma↗
PubMed1997

Histologic, molecular, and radiologic characterization of resolving cerebral posttransplant lymphoproliferative disorder.

Lymphoproliferative disorders (LPDs) are commoner in pediatric versus adult immunosuppressed transplant recipients, and frequently involve the central nervous system. In these circumstances, the justification for biopsy is heavily influenced by the likely diagnostic yield. The present study centers on a 12-y-old renal transplant patient who developed multifocal cerebral LPD and had serial magnetic resonance (MR) examinations during the course of her illness from which she has completely recovered upon reduction of immunosuppression. She underwent stereotaxic biopsy, which was analyzed by both immunocytochemistry and polymerase chain reaction to examine the general question of how to release the maximum amount of information contained within, as well as to obtain a tissue diagnosis in this particular case. We show that a combination of these methods permits identification of the immunophenotype, lineage, clonality, viral involvement, and origin of abnormal cellular infiltrates. The biopsy also showed a novel histologic pattern of LPD, comprising numerous benign T cells obscuring a tiny clone of B cells. The MR examinations documented, for the first time, the differences in signal that accompany clinical resolution at both biopsied and nonbiopsied sites, showing that the latter may be associated with reduction, but not elimination, of MR signal abnormality. We conclude: 1) a combination of conventional and polymerase chain reaction analysis offers the greatest diagnostic yield from stereotaxic biopsies, even when the available tissue is minimal; 2) a focal polyclonal T cell infiltrate should prompt further investigation to exclude an underlying B cell lesion.

Adult↗
PubMed1995

Hippocampal neuronal atrophy occurs in rhesus macaques following infection with simian immunodeficiency virus.

There is strong evidence that patients with AIDS have loss of cortical neurons. In this study we have examined the hippocampus of rhesus monkeys infected with simian immunodeficiency virus (SIV) to determine whether neuronal damage occurs in this model of human AIDS and to investigate its time course. Twenty-eight infected monkeys (23 young [< 9 years] and five elderly [> 16 years]) were compared with 11 controls (six young and five elderly). Numbers of nucleolated neurons per unit area of section and mean pyramidal cell diameters were measured in each CA sub-field of each animal. There was neuronal atrophy in all regions examined, as early as 3 months following inoculation. An initial apparent increase in neuronal density at 3 months did not reach statistical significance. In younger animals, however, there was a later, significant association between the reduction in neuronal density and duration of infection. Elderly animals were only examined at a single, early time point. These results show that there is neuronal pathology following infection with SIV and that there is probably subsequent neuronal death.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Different patterns of neuropathological disease in rhesus monkeys infected by simian immunodeficiency virus, and their relation to the humoral immune response.

The brains of 21 rhesus monkeys inoculated with SIVMAC251 were examined after intervals ranging from 3 to 27 months and compared with five uninoculated controls. Eighteen animals became infected and individually exhibited several distinct patterns of disease. Nine (50%) had largely intramural leptomeningeal venous infiltrates (LMVI) without multinucleate giant cells (MGC) or foamy macrophages. Three (17%) had only MGC lesions, involving the cerebral parenchyma. One had both patterns and five (33%) neither. The controls had sparse and tiny LMVI only, similar to three inoculated animals that did not become infected. Immunohistochemistry showed the predominance of T and B lymphocytes in LMVI and choroid plexus mononuclear lesions but a predominance of macrophages over lymphocytes in the MGC lesions. Specific disease patterns differed in their association with the humoral immune response. Animals with LMVI were all hypergammaglobulinaemic when killed compared to pre-inoculation levels, and the size of the change in serum immunoglobulin concentration was positively correlated with a quantitative index of LMVI density. Furthermore, their post-mortem lymph node histology was hyperplastic. In contrast, animals found at autopsy to have MGC brain lesions were hypogammaglobulinaemic compared to preinoculation. The results are consistent with two phases in SIV-associated disease: one characterized by LMVI and hypergammaglobulinaemia and another featuring MGC and hypogammaglobulinaemia.

Animals↗
PubMed1993

Cerebral aspergilloma in a child with autosomal recessive chronic granulomatous disease.

A 2 year old girl presented with epilepsy 16 months after being diagnosed as having autosomal recessive chronic granulomatous disease. Computed tomography showed a cerebral mass which was surgically removed and proved histologically to be an aspergilloma. This case illustrates the application of molecular diagnostic techniques to the diagnosis of chronic granulomatous disease. The occurrence of, and unusual reaction to, cerebral aspergillus infection indicates the need to consider this possibility in the differential diagnosis of mass lesions in chronic granulomatous disease. Furthermore, it is clear that autosomal recessive chronic granulomatous disease cannot be considered to be a clinically mild form that is exempt from major neurological complications.

Aspergillosis↗
PubMed1991

Evaluation of a linear model of directional selectivity in simple cells of the cat's striate cortex.

We have compared the responses of simple cells to laterally moving sinusoidal gratings and to stationary temporally-modulated gratings. From the amplitudes and temporal phases of the responses to stationary gratings of different spatial phases, it should be possible to predict the preferred direction of movement, the amplitudes of the responses to gratings moving in the preferred and nonpreferred directions and, thence, the degree of directional preference (Reid et al., 1987). The preferred direction can be predicted reliably. However, the magnitude of the directional preference cannot be predicted, since the measured amplitude of the response in the nonpreferred direction of movement is very much less than that predicted by a linear theory. Nonlinearities in the relationship between response amplitude and contrast may contribute to the failure of the predictions, but this contribution is small. We conclude that the magnitude of the directional preference seems to be determined predominantly by nonlinear suppression of the response in the nonpreferred direction of movement.

Animals↗
PubMed1990

The effects of contrast on the linearity of spatial summation of simple cells in the cat's striate cortex.

Non-linearities of spatial summation were examined in simple cells in the cat's striate cortex. The degree of non-linearity was assessed from an examination of the waveforms of the responses to moving sinusoidal gratings and was quantified by a measure called relative modulation. Relative modulation was affected little by changes in contrast at either optimal or non-optimal spatial frequencies. The non-linearities of spatial summation exhibited by some simple cells are, therefore, essential. Those simple cells which exhibit linear spatial summation are no less linear at high stimulus contrasts. These results support a 'push-pull' model of simple cell receptive field organization in which ON and OFF centre l.g.n. input is combined both additively and subtractively.

Animals↗
PubMed1987

Spatial summation by simple cells in the striate cortex of the cat.

Spatial summation has been studied in simple cells of the cat's visual cortex by examining the responses of pairs of lines. One line was placed in an ON region of the receptive field; the other was placed in an OFF region. When the luminances of the lines were modulated in anti-phase, the excitatory responses to the individual lines were almost synchronous. A simple cell's overt response to the composite stimulus was usually greater than the sum of the overt responses to the two components. The result could be explained by supposing that the underlying response was the linear sum of the excitatory signals but that an overt response occurred only when the underlying response exceeded a fixed threshold value. This was true even of simple cells which exhibited non-linearities of spatial summation, as judged from the waveforms of their responses to moving sinusoidal gratings. When the two lines were modulated in phase, the excitatory responses occurred in different halves of the temporal cycle. Some cells summed antagonistic signals linearly. The waveforms of their responses to moving sinusoidal gratings also implied linear spatial summation. However, other cells whose responses to moving gratings implied linearity of summation did not, in fact, sum antagonistic signals linearly. The excitatory responses evoked in a receptive field region were weaker than the inhibitory responses that could be evoked in the same region. The remaining cells did not sum antagonistic signals linearly. There was imperfect cancellation, resulting in the generation of ON-OFF response components. The excitatory responses evoked in a receptive field region were stronger than the inhibitory responses that could be evoked in the same region. These cells gave responses to sinusoidal gratings that did imply nonlinear spatial summation.

Animals↗
PubMed1986

Factors influencing the temporal phase of response to bar and grating stimuli for simple cells in the cat striate cortex.

We have characterized the speed of response of simple cells in cat striate cortex by the temporal phase of the response to bar and grating stimuli. Stimulation of the most responsive subregion (either ON or OFF) in the receptive field with a 1 Hz temporally modulated bar elicited responses whose phase led the excitatory phase of the stimulus by about 25 degrees. The response to stationary gratings whose contrast was sinusoidally modulated at 2 Hz also showed a phase lead. The differences in the phase of response of ON and OFF sub-regions exhibited a marked scatter about the expected value of 180 degrees. The phase of response to both temporally modulated bars and laterally moving gratings advanced by 20-35 degrees as the stimulus contrast was raised by a factor of 5.

Animals↗