Biomedical subjects

T C Cox

Publications and source records attributed to T C Cox.

At least 19 recordsLinked to original sources

PubMed2000

Thalamic changes with mesial temporal sclerosis: MRI.

We reviewed the preoperative images of 28 patients with pathologically proven mesial temporal sclerosis, to assess thalamic asymmetry and signal change. A further 25 nonsurgical patients with temporal lobe epilepsy and unequivocal, unilateral changes of mesial temporal sclerosis, and 20 controls, were also reviewed. None of the control group had unequivocal asymmetry of the thalamus. There was an ipsilateral asymmetrically small thalamus in five (18%) of the surgical group and in three (12%) of the nonsurgical patients. In four cases there was thalamic signal change. In three patients with thalamic volume loss there was ipsilateral hemiatrophy. All patients with an asymmetrically small thalamus had an asymmetrically small fornix and all but one a small ipsilateral mamillary body.

Adult↗

PubMed2000

Voxel similarity measures for 3-D serial MR brain image registration.

We have evaluated eight different similarity measures used for rigid body registration of serial magnetic resonance (MR) brain scans. To assess their accuracy we used 33 clinical three-dimensional (3-D) serial MR images, with deformable extradural tissue excluded by manual segmentation and simulated 3-D MR images with added intensity distortion. For each measure we determined the consistency of registration transformations for both sets of segmented and unsegmented data. We have shown that of the eight measures tested, the ones based on joint entropy produced the best consistency. In particular, these measures seemed to be least sensitive to the presence of extradural tissue. For these data the difference in accuracy of these joint entropy measures, with or without brain segmentation, was within the threshold of visually detectable change in the difference images.

Adult↗

PubMed2000

Sources of error in comparing functional magnetic resonance imaging and invasive electrophysiological recordings.

OBJECT: Several authors have recently reported studies in which they aim to validate functional magnetic resonance (fMR) imaging against the accepted gold standard of invasive electrophysiological monitoring. The authors have conducted a similar study, and in this paper they identify and quantify two characteristics of these data that can make such a comparison problematic. METHODS: Eight patients in whom surgery for epilepsy was performed and five healthy volunteers underwent fMR imaging to localize the part of the sensorimotor cortex responsible for hand movement. In the patient group subdural electrode mats were subsequently implanted to identify eloquent regions of the brain and the epileptogenic zone. The fMR imaging data were processed to correct for motion during the study and then registered with a postimplantation computerized tomography (CT) scan on which the electrodes were visible. The motion during imaging in the two groups studied, and the deformation of the brain between the preoperative images and postoperative scans were measured. The patients who underwent epilepsy surgery moved significantly more during fMR imaging experiments than healthy volunteers performing the same motor task. This motion had a particularly increased out-of-plane component and was significantly more correlated with the stimulus than in the volunteers. This motion was especially increased when the patients were performing a task on the side affected by the lesion. The additional motion is hard to correct and substantially degrades the quality of the resulting fMR images, making it a much less reliable technique for use in these patients than in others. Also, the authors found that after electrode implantation, the brain surface can shift more than 10 mm relative to the skull compared with its preoperative location, substantially degrading the accuracy of the comparison of electrophysiological measurements made in the deformed brain and fMR studies obtained preoperatively. CONCLUSIONS: These two findings indicate that studies of this sort are currently of limited use for validating fMR imaging and should be interpreted with care. Additional image analysis research is necessary to solve the problems caused by patients' motion and brain deformation.

Cerebral Cortex↗

PubMed1999

FXY2/MID2, a gene related to the X-linked Opitz syndrome gene FXY/MID1, maps to Xq22 and encodes a FNIII domain-containing protein that associates with microtubules.

Opitz G/BBB syndrome (OS) is a genetically heterogeneous disorder with an X-linked locus and an autosomal locus linked to 22q11.2. OS affects multiple organ systems with often variable severity even between siblings. The clinical features, which include hypertelorism, cleft lip and palate, defects of cardiac septation, hypospadias, and anorectal anomalies, indicate an underlying disturbance of the developing ventral midline of the embryo. The gene responsible for X-linked OS, FXY/MID1, is located on the short arm of the human X chromosome within Xp22.3 and encodes a protein with both an RBCC (RING finger, B-box, coiled coil) and a B30.2 domain. The Fxy gene in mice is also located on the X chromosome but spans the pseudoautosomal boundary in this species. Here we describe a gene closely related to FXY/MID1, called FXY2, which also maps to the X chromosome within Xq22. The mouse Fxy2 gene is located on the distal part of the mouse X chromosome within a region syntenic to Xq22. Analysis of genes flanking both FXY/MID1 and FXY2 (as well as their counterparts in mouse) suggests that these regions may have arisen as a result of an intrachromosomal duplication on an ancestral X chromosome. We have also identified in both FXY2 and FXY/MID1 proteins a conserved fibronectin type III domain located between the RBCC and B30.2 domains that has implications for understanding protein function. The FXY/MID1 protein has previously been shown to colocalize with microtubules, and here we show that the FXY2 protein similarly associates with microtubules in a manner that is dependent on the carboxy-terminal B30.2 domain.

Abnormalities, Multiple↗

PubMed1999

Hippocampal involvement in spatial and working memory: a structural MRI analysis of patients with unilateral mesial temporal lobe sclerosis.

Forty-seven patients with unilateral temporal lobe epilepsy (TLE) were investigated on the Nine-Box Maze. The task was designed to compare working memory and spatial mapping theories of the functions of the hippocampus and provide measures of spatial, object, working, and reference memory. The results extended our previous findings in a larger group of patients. Spatial memory deficits across both working and reference memory conditions were found in patients with a right epileptogenic focus. There was no evidence of an object working memory deficit, but a nonlateralized impairment in object reference memory was revealed, which is consistent with our previous findings. The pattern of results was confirmed in a subgroup of 33 patients with unilateral atrophy localized to the hippocampus and parahippocampal gyrus, as verified by volumetric analysis of magnetic resonance images. In addition spatial memory errors significantly correlated with volumetric measures of mesial temporal lobe structures and not with measures of the remaining temporal cortex. In contrast, object reference memory errors correlated with volumetric measures of the temporal cortex and not with mesial temporal lobe structures. These findings support a specialized role for the right hippocampal region in spatial memory.

Adult↗

PubMed1999

Congenital varicella syndrome: cranial MRI in a long-term survivor.

Congenital varicella syndrome is a rare disorder which follows maternal infection in the first or early second trimester. The syndrome comprises a number of malformations including microcephaly, cortical destruction and limb hypoplasia. We describe a case where there has been long-term survival following second trimester maternal infection. The clinical findings, including the characteristic lower limb hypoplasia, are documented, as are the appearances on cranial MRI indicating an encephaloclastic porencephaly.

Abnormalities, Multiple↗

PubMed1999

Tentorial dural arteriovenous fistulae: endovascular treatment with transvenous coil embolisation.

Tentorial arteriovenous dural fistulae are uncommon. They are aggressive lesions: of all intracranial dural fistulae they are the most likely to present with haemorrhage. Treatment options include surgical excision or interruption of leptomeningeal draining veins and arterial embolisation in isolation or in combination with surgery. There has been one case report of treatment by percutaneous transvenous coil embolisation. We describe successful transvenous coil embolisation of two tentorial dural fistulae presenting with subarachnoid haemorrhage.

Arteriovenous Fistula↗

PubMed1999

Intrasphenoid cephalocele: MRI in two cases.

The intrasphenoid form of basal cephalocele is uncommon. We describe the clinical, CT and MRI findings in two cases presenting in middle age with persistent cerebrospinal fluid rhinorrhoea. Emphasis is placed upon the imaging findings which aid in discrimination of intrasphenoidal cephalocele from more common causes of a sphenoid sinus mass.

Adult↗

PubMed1999

MRI of the brain in HIV-positive patients: what is the value of routine intravenous contrast medium?

Our purpose was to assess the value of routine administration of intravenous gadolinium-DTPA (Gd-DTPA) for cranial MR in a series of human immunodeficiency virus (HIV)-positive patients. Two radiologists retrospectively reviewed 150 consecutive examinations of 104 patients. All patients underwent unenhanced and contrast-enhanced images. Each radiologist independently assessed first the unenhanced images alone and then the pre- and postinjection images together. Then both reviewed the complete study and produced a consensus report. The history, investigations and management were collated separately and were unknown to the radiologists. Contrast-enhanced T1-weighted images showed new focal abnormalities, not seen on the T2-weighted or unenhanced images in 15 (14 %) patients, but almost always in the context of abnormal unenhanced images. In only 2 patients (2 %) did contrast medium reveal abnormalities when the unenhanced study had been considered normal. In only 1 of these (1 %) was the new finding, cytomegalovirus diffuse ependymal enhancement, of clinical importance, although the diagnosis of encephalitis was made on routine examination of cerebrospinal-fluid. The other revealed a toxoplasma lesion in a patient known to have resolving disease. Meningeal disease not suspected on the unenhanced images was shown in 2 patients (2 %). In these case the unenhanced images were abnormal in other respects. Intravenous Gd-DTPA was helpful to the radiologist in making a radiological diagnosis in 11 patients (11 %), usually by improving characterisation of a lesion seen on the unenhanced images. The contribution of intravenous Gd-DTPA in this series does not warrant recommending its use in every case.

AIDS Dementia Complex↗

PubMed1999

Calcium and ATP regulation of ion transport in larval frog skin.

Ion transport measured as short circuit current (Isc) across the skin of larval frogs is activated by amiloride, acetylcholine, and ATP. In many epithelia, ATP stimulation of Isc involves an increase in intracellular calcium. To define the role of changes in intracellular calcium in ATP stimulation of Isc in larval frog skin, epithelial cells were loaded with calcium by adding 5 microM ionomycin to a 2 mM calcium apical Ringer's solution. Calcium loading had no observable effect on baseline Isc or on stimulation by ATP. Minimizing changes in intracellular calcium by loading the cell with the calcium chelator BAPTA also had no measurable effect on ATP stimulation of Isc. When the apical side was bathed with Ca(2+)-free Ringer's solution, ionomycin increased Isc up to 15 microA. This increase was partially blocked by 2 mM Ca2+, 2 mM Mg2+, and 10 microM W-7. Other experiments showed that baseline-stimulated and ATP-stimulated Isc were always larger in 2 mM Mg2+ Ringer's compared to 2 mM Ca2+. In dissociated cells bathed in 2 mM Ca2+ Ringer's, ATP had no effect on intracellular calcium as measured by Fluo-LR fluorescence changes. In conclusion, ATP apparently stimulates Isc without concomitant changes in intracellular calcium. This is consistent with a directly ligand-gated receptor at the apical membrane with P2X-like characteristics.

Adenosine Triphosphate↗

PubMed1999

Comparison of intra-arterial digital subtraction angiography, magnetic resonance angiography and duplex ultrasonography for measuring carotid artery stenosis.

BACKGROUND: Duplex ultrasonography and magnetic resonance angiography (MRA) are becoming competitive alternatives to angiography for determining the degree of internal carotid artery (ICA) stenosis. Varying reports have been published regarding the suitability of each technique for grading ICA disease. This retrospective study compared the merits of these three modalities for measuring ICA stenosis. METHODS: One hundred and eleven patients being considered for carotid endarterectomy underwent intra-arterial digital subtraction angiography (DSA) via arch injection. Duplex imaging was performed in all patients and MRA in 50. The degree of carotid stenosis estimated by the three modalities was compared. RESULTS: There was good correlation between subjectively graded MRA and DSA images (r = 0.87, P < 0.001, n = 82 carotids) but poor correlation for objective estimates. MRA tended to underestimate the degree of stenosis (bias - 4.5 per cent) compared with DSA, but showed good correlation with duplex ultrasonography estimates (r = 0. 86, P < 0.001, n = 87 carotids). Both non-invasive modalities produced high values of sensitivity and specificity in estimating stenoses of greater than 70 per cent. MRA was less sensitive for distinguishing between severe stenosis and complete occlusion. CONCLUSION: This study did not resolve the debate regarding the method of choice as both MRA and duplex ultrasonography were accurate for imaging carotid stenoses.

Aged↗

PubMed1999

Stereo augmented reality in the surgical microscope.

We present an augmented reality system that allows surgeons to view features from preoperative radiological images accurately overlaid in stereo in the optical path of a surgical microscope. The purpose of the system is to show the surgeon structures beneath the viewed surface in the correct 3-D position. The technical challenges are registration, tracking, calibration and visualisation. For patient registration, or alignment to preoperative images, we use bone-implanted markers and a dental splint is used for patient tracking. Both microscope and patient are tracked by an optical localiser. Calibration uses an accurately manufactured object with high contrast circular markers which are identified automatically. All ten camera parameters are modelled as a bivariate polynomial function of zoom and focus. The overall system has a theoretical overlay accuracy of better than 1 mm. Implementations of the system have been tested on seven patients. Recent measurements in the operating room conformed to our accuracy predictions. For visualisation the system has been implemented on a graphics workstation to enable high frame rates with a variety of rendering schemes. Several issues of 3-D depth perception remain unsolved, but early results suggest that perception of structures in the correct 3-D position beneath the viewed surface is possible.

Depth Perception↗

PubMed1998

Identification and characterization of a conserved erythroid-specific enhancer located in intron 8 of the human 5-aminolevulinate synthase 2 gene.

Thirty five kilobases of sequence encompassing the human erythroid 5-aminolevulinate synthase (ALAS2) gene have been determined. Analysis revealed a very low GC content, few repetitive elements, and evidence for the insertion of a reverse-transcribed mRNA sequence and a neighboring gene. We have investigated whether introns 1, 3, and 8, which correspond to DNase I-hypersensitivity sites in the structurally related mouse ALAS2 gene, affect expression of the human ALAS2 promoter in transient expression assays. Whereas intron 3 was marginally inhibitory, introns 1 and 8 of the human gene stimulated promoter activity. Intron 8 harbored a strong erythroid-specific enhancer activity which was orientation-dependent. Deletion analysis of this region localized enhancer activity to a fragment of 239 base pairs. Transcription factor binding sites clustered within this region include GATA motifs and CACCC boxes, critical regulatory sequences of many erythroid cell-expressed genes. These sites were also identified in the corresponding intron of both the murine and canine ALAS2 genes. Mutagenesis of these conserved sites in the human intron 8 sequence and transient expression analysis in erythroid cells established the functional importance of one GATA motif and two CACCC boxes. The GATA motif bound GATA-1 in vitro. The two functional CACCC boxes each bound Sp1 or a related protein in vitro, but binding of the erythroid Krüppel-like factor and the basic Krüppel-like factor could not be detected. The intron 8 enhancer region was not activated by GATA-1 together with Sp1 in transactivation experiments in COS-1 cells indicating the involvement of a related Sp1 protein or of another unidentified erythroid factor. Overall, these results demonstrate that a GATA-1-binding site and CACCC boxes located within the human ALAS2 intron 8 are critical for the erythroid-specific enhancer activity in transfected erythroid cells, and due to the conserved nature of these binding sites across species, it seems likely that these sites play a functional role in the tissue-restricted expression of the gene in vivo.

5-Aminolevulinate Synthetase↗

PubMed1998

Magnetic resonance imaging features of pituitary yttrium-90 rod implantation.

Intersellar implantation of yttrium-90 rods was a common treatment for a variety of pituitary tumours in the 1960s and 1970s. The magnetic resonance (MR) imaging features in three patients with implants (two for growth hormone-secreting and one for prolactin-secreting pituitary adenomas) are presented: the implants appeared as low signal cylinders with no image distortion, in contradistinction to CT where the implants generate beam hardening and back projection artefacts. Confident evaluation of the pituitary fossa for residential tumour and sequelae of therapy could be made on MR. It is the imaging technique of choice in the follow-up of patients treated with yttrium-90 implants.

Adenoma↗

PubMed1998

Rasmussen's encephalitis: neuroimaging findings in 21 patients with a closer look at the basal ganglia.

Rasmussen's encephalitis usually presents in childhood. The clinical picture in Rasmussen's disease is protean, and the findings from direct brain imaging help to explain the variations seen in this syndrome. The role and involvement of the basal ganglia in this condition is clarified by comparing the changes seen on computerised tomography and magnetic resonance imaging with the clinical details of 21 patients described in this retrospective study.

Adolescent↗

PubMed1998

Funny turns.

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Cerebrospinal Fluid Rhinorrhea↗

PubMed1997

Transcriptional regulation of the human erythroid 5-aminolevulinate synthase gene. Identification of promoter elements and role of regulatory proteins.

We have characterized the 5'-flanking region of the human erythroid-specific 5-amino levulinate synthase (ALAS) gene (the ALAS2 gene) and shown that the first 300 base pairs of promoter sequence gives maximal expression in erythroid cells. Transcription factor binding sites clustered within this promoter sequence include GATA motifs and CACCC boxes, critical regulatory sequences of many erythroid cell-expressed genes. GATA sites at -126/-121 (on the noncoding strand) and -102/-97 were each recognized by GATA-1 protein in vitro using erythroid cell nuclear extracts. Promoter mutagenesis and transient expression assays in erythroid cells established that both GATA-1 binding sites were functional and exogenously expressed GATA-1 increased promoter activity through these sites in transactivation experiments. A noncanonical TATA sequence at the expected TATA box location (-30/-23) bound GATA-1- or TATA-binding protein (TBP) in vitro. Conversion of this sequence to a canonical TATA box reduced expression in erythroid cells, suggesting a specific role for GATA-1 at this site. However, expression was also markedly reduced when the -30/-23 sequence was converted to a consensus GATA-1 sequence (that did not bind TBP in vitro), suggesting that a functional interaction of both factors with this sequence is important. A sequence comprising two overlapping CACCC boxes at -59/-48 (on the noncoding strand) was demonstrated by mutagenesis to be functionally important. This CACCC sequence bound Sp1, erythroid Krüppel-like factor, and basic Krüppel-like factor in vitro, while in transactivation experiments erythroid Krüppel-like factor activated ALAS2 promoter expression through this sequence. A sequence at -49/-39 with a 9/11 match to the consensus for the erythroid specific factor NF-E2 was not functional. Promoter constructs with 5'-flanking sequence from 293 base pairs to 10.3 kilobase pairs expressed efficiently in COS-1 cells as well as in erythroid cells, indicating that an enhancer sequence located elsewhere or native chromatin structure may be required for the tissue-restricted expression of the gene in vivo.

5-Aminolevulinate Synthetase↗

PubMed1997

Apical regulation of nonselective cation channels by ATP in larval bullfrog skin.

The apical membrane of larval bullfrog skin contains a nonselective cation channel that can be activated by apically applied amiloride and acetylcholine. In our search for other ligands that might activate this channel, ATP and other purinergics were tested. When ATP (10-1,000 microM) was added to the apical side of tadpole skin mounted in a modified Ussing chamber, there was a transient increase in short circuit current (Isc). The increase in Isc occurred with either Na or K as the dominant cation in the apical solution. The response was larger in a calcium-free Ringer. ADP and AMP had similar but smaller effects than ATP. Adenosine and UTP were without effect. The ATP response was blocked by W-7, atropine, curare, diltiazem, and suramin. These blockers also inhibit amiloride stimulation of Isc, suggesting that ATP activates a related transport pathway. Studies with analogs of ATP suggest that the ATP binding site in tadpole skin has characteristics in common with the P2x receptor found in other tissues. These results demonstrate that in addition to amiloride and acetylcholine, ATP stimulates cation transport at the apical membrane of larval amphibian skin epithelia.

Acetylcholine↗