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T Cox

Publications and source records attributed to T Cox.

At least 37 records · Page 2Linked to original sources
PubMed2000

Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis.

BACKGROUND: Current treatment for Gaucher's disease involves administration of intravenous glucocerebrosidase to degrade glucocerebroside stored in lysosomes. Lowering the rate of biosynthesis of glucocerebroside should decrease accumulation of this substrate. We investigated the safety and efficacy of OGT 918 (N-butyldeoxynojirimycin), an inhibitor of glucosyltransferase, as a novel oral treatment for non-neuronopathic Gaucher's disease. METHODS: We recruited, into a 1-year open-label study, 28 adults (seven with previous splenectomies) from four national Gaucher's referral clinics, who were unable or unwilling to receive enzyme treatment. We measured liver and spleen volume by computed tomography or magnetic resonance imaging at baseline and at months 6 and 12, and biochemical and haematological variables monthly, including chitotriosidase activity (a sensitive marker of Gaucher's disease activity). Patients were started on 100 mg oral OGT 918 three times daily. FINDINGS: Baseline liver volumes were 1.1-2.7 times normal and spleen volumes 5.1-24.8 times normal. At 12 months, mean liver and spleen volumes were significantly lowered by 12% (95% CI 7.8-16.4) and 19% (14.3-23.7), respectively (each p<0.001). Haematological variables improved slightly. Mean organ volume and blood counts improved continually between 6 months and 12 months of treatment. Mean chitotriosidase concentrations fell by 16.4% over 12 months (p<.0001). Six patients withdrew because of gastrointestinal complaints (two), personal reasons (two), or severe pre-existing disease (two). The most frequent adverse effect was diarrhoea, which occurred in 79% of patients shortly after the start of treatment. INTERPRETATION: Decrease of substrate formation by OGT 918 improves key clinical features of non-neuronopathic Gaucher's disease. The strategy justifies further trials in this and other glycosphingolipid storage disorders.

1-Deoxynojirimycin↗
PubMed2000

Sequence analysis of bacterial DNA in the colon and stomach of the Tyrolean Iceman.

The male human body found in an Alpine glacier on September 19, 1991 ("Tyrolean Iceman") has, for the first time in history, given scientists a chance to perform detailed anatomical, histological, and molecular investigations on the organs of a person from the Neolithic Age (5350-5100 B.P.). In the present study, tissue samples aseptically taken from the stomach and the colon of the mummy were utilized for DNA extraction, and the DNA was PCR-amplified, using primer pairs designed to bind to fragments of the 16s ribosomal RNA gene (16s rDNA) of a broad range of bacteria. The PCR products were cloned in plasmid vectors, and the recombinant clones (amplicons) were sequenced. The sequence data were finally used for scanning data libraries containing the corresponding sequences of present-day bacteria, to infer the putative ecophysiology of the ancient ones. The same procedure was repeated on some fragments of grass from the clothing found near the corpse. These fragments were taken as a control of the microbiological situation of the glacier. The results show that the flora of the Iceman's stomach is entirely composed of Burkholderia pickettii, an organism commonly found in aquatic habitats. The colon, on the other hand, contains several members of the fecal flora of humans, such as Clostridium perfringens, C. ghonii, C. sordellii, Eubacterium tenue, and Bacteroides sp. The Iceman's colon, however, was found to contain, rather unexpectedly, also some members of the genus Vibrio. The results are discussed in light of what is known about the preservation of microbial DNA at the Iceman's site and of previous parasitological studies performed on the Iceman himself and on human coprolites.

Animals↗
PubMed2000

Cerebellar ataxia, anterior horn cell disease, learning difficulties, and dystonia: a new syndrome.

The following case reports describe a new condition of cerebellar ataxia, anterior horn cell disease, dystonia, and learning difficulties. Four cases are described. The condition appears to be of autosomal recessive inheritance as the group is made up of two pairs of sisters. All cases were evident by 3 years of age. Anterior horn cell disease was of a type not previously described at this age in association with cerebellar ataxia. Further genetic studies suggest the condition is not allelic with spinal muscular atrophy having no evidence of deletion of the survival motor neurone gene.

Adolescent↗
PubMed2000

Haemochromatosis: novel gene discovery and the molecular pathophysiology of iron metabolism.

The application of molecular genetics to haemochromatosis and experimental mutagenesis in animals has transformed our capacity to investigate the unique physiology of iron homeostasis-a key problem in biology and medicine. The identification of HFE, the principal determinant of adult haemochromatosis (HFE1; OMIM 235200) and TfR2, recently implicated in a rarer form of the inherited disorder (HFE3; OMIM 604250), and the promise of candidate genes for juvenile haemochromatosis (HFE2; OMIM 602390) and neonatal haemochromatosis (OMIM 231100) provide the foundation for important studies into the control mechanism of iron balance in humans. The rare conditions atransferrinaemia (OMIM 209300) and acaeruloplasminaemia (OMIM 604290), each associated with tissue iron overload, have already implicated the iron transport ligand transferrin and the copper transporter caeruloplasmin in the control of iron homeostasis. Gene mapping studies in animal mutants with anaemia due to defects in the uptake or tissue transfer of iron have yielded novel proteins involved in iron transport: DMT1 (brush border transporter of ferrous iron) in the mk/mk mouse, hephaestin (basolateral multi-copper ferroxidase) in the sex-linked anaemic mouse (sla) and ferroportin1 (basolateral iron exporter) in zebrafish weh mutants. The discovery of genes that determine heritable defects of iron absorption and regulation in animals and humans thus holds promise for a complete mechanistic understanding of the molecular pathophysiology of iron metabolism.

Forecasting↗
PubMed2000

Unilateral lesions of the globus pallidus: report of four patients presenting with focal or segmental dystonia.

OBJECTIVES: To interpret clinical features after unilateral lesions of the globus pallidus on the basis of physiology of the basal ganglia. METHODS: Four patients with unilateral lesions in the globus pallidus (GP) were clinically examined and the literature on patients with pallidal lesions was reviewed. RESULTS: Three patients presented with contralateral dystonia largely confined to one arm in one case and one leg in two cases. One patient had predominant contralateral hemiparkinsonism manifested mainly as micrographia and mild dystonia in one arm. The cause of the lesions was unknown in two patients. In the other two symptoms had developed after head trauma and after anoxia. All lesions involved the internal segment of the GP. Two patients, including the patient with hemiparkinsonism, had additional involvement of the external segment of the GP. In the literature reports on 26 patients with bilateral lesions restricted to the GP only two with unilateral lesions were found. The patients with bilateral pallidal lesions manifested with dystonia, parkinsonism, or abulia. One of the patients with unilateral GP lesions had contralateral hemidystonia, the other contralateral arm tremor. CONCLUSION: These cases emphasise the importance of the GP, particularly its internal segment, in the pathophysiology of dystonia.

Adult↗
PubMed2000

Positron emission tomography in imaging spinal cord tumors.

The ability of positron emission tomography (PET) to detect spinal cord tumors was studied prospectively in 14 patients presenting over a 5-year period. Abnormal uptake by [18F]-fluorodeoxyglucose (FDG) or 11C-methionine was detected in all except one. These data were assessed in relation to magnetic resonance imaging (MRI) findings with regard to tumor type and extent preoperatively, findings at operation, and subsequent clinical course. The group consisted of six astrocytomas, five ependymomas, one mixed ependymoma and astrocytoma, one schwannoma, and one ganglioglioma, all confirmed histologically. This is the largest study comparing spinal PET to MRI. Accurate preoperative correlation between PET and MRI was found in all eight patients scanned at first presentation. The PET uptake was in keeping with the low-grade histology of the tumors. Postoperatively, PET and MRI findings were in agreement in nine patients. In eight of these the findings were in keeping with the subsequent clinical course. In three patients, however, the PET findings were at variance with the clinical course and MRI findings. In one, persistent FDG uptake after radiotherapy was seen where there was subsequent tumor resolution. In two patients with low-grade astrocytomas, scanned with FDG and 11C-methionine, respectively, tracer was not taken up by residual tumor. In this small group of patients, PET did not provide additional useful information. This could be because all tumors studied were low grade and the limited spatial resolution of PET does not lend itself to imaging small spinal cord tumors. The prospective study of larger numbers of patients with a wider range of tumor types is required, but this might be difficult to achieve given the rarity of spinal cord tumors.

Adolescent↗
PubMed2000

Effects of three different doses of a bolus injection of gadodiamide: assessment of regional cerebral blood volume maps in a blinded reader study.

BACKGROUND AND PURPOSE: Reconstruction of first-pass bolus information to derive regional cerebral blood volume (rCBV) maps is commonly performed in many centers; however, various protocols with different doses of paramagnetic contrast injections have been reported. We evaluated the dose dependency of rCBV maps in a brain tumor population by using three different doses of gadodiamide injection to evaluate their diagnostic accuracy in blinded reader sessions. METHODS: Eighty-three patients with intraaxial brain tumors (72 gliomas) were studied at three centers and randomized to receive a bolus injection of 0.1, 0.2, or 0.3 mmol/kg per body weight of gadodiamide. rCBV maps were generated from T2*-weighted gradient-echo echoplanar sequences at 1.5 T. Data processing was performed according to the indicator dilution theory. RESULTS: The mean contrast-to-noise ratio (CNR) was significantly different between gadodiamide doses of 0.1 and 0.2 mmol/kg (CNR = 8.7 and 15.7) and between 0.1 and 0.3 mmol/kg (CNR = 17.7). No significant difference was found between doses of 0.2 and 0.3 mmol/kg. Sensitivity for the differentiation of benign and malignant brain tumors was 80%, 95%, and 91%, and specificity was 45%, 54%, and 43% by blinded readings at 0.1, 0.2, and 0.3 mmol/ kg, respectively, as compared with histologic findings. Nonblinded readings had a sensitivity of 83%, 100%, and 90% and a specificity of 82%, 100%, and 73% at 0.1, 0.2, and 0.3 mmol/kg, respectively. CONCLUSION: A dose of 0.2 mmol/kg of gadodiamide is recommended for reconstruction of rCBV maps if data are acquired with the T2*-weighted protocol described.

Blood Volume↗
PubMed1999

Diversity of Microorganisms Isolated from Amber.

> Abstract Claims that organisms can be cultured from amber, if substantiated, would be significant contributions to our understanding of the evolution, tenacity, and potential spread of life. Three reports on the isolation of organisms from amber have been published. Cano and Borucki recently reported the isolation of Bacillus sphaericus and Lambert et al. have described a new species designated Staphylococcus succinus from 25-40 million year old Dominican amber. These characterized organisms were phylogenetically distant from extant relatives and the Staphylococcus sp. sufficiently far removed from other extant staphylococci to be considered a new species. Here we report the culture of bacteria from Dominican and previously untested 120 million year old Israeli (Lebanese lode) amber. Twenty-seven isolates from the amber matrix have been characterized by fatty-acid profiles (FAME) and/or 16S rRNA sequencing. We also performed a terminal restriction fragment pattern (TRF) analysis of the original amber before prolonged culture by consensus primer amplification of the 16S rRNA followed by restriction enzyme digestion of the amplicons. Sample TRFs were consistent with a sparse bacterial assemblage and included at least five of the isolated organisms. Finally, we microscopically mapped the internal topography of an amber slice.http://link.springer-ny.com/link/service/journals/00248/bibs/38n1p58.html

Journal Article↗
PubMed1999

System memory in violent incidents: evidence from patterns of reoccurrence.

For 20% of a sample of 1,078 violent incidents reported in British bars and pubs, another incident was reported at the same premises within 6 months. Log-survival analysis revealed nonrandom sequences that demonstrate a system memory effect separate from any biases involving particular venues. The rate of reoccurrence was not constant during the 6 months following incidents but was significantly higher for Weeks 1-4, approximated to the mean value for Weeks 5-12, and declined for Weeks 13-26. Reoccurrence was particularly likely in the first 3-4 days after an incident. Risk of reoccurrence was further increased for incidents that involved either threats or the exit and return of the assailants within that original incident. Results support the view that "violence breeds violence" and demonstrate the need for increased staff vigilance for up to 12 weeks following a violent incident, and particularly during the first few days and weeks.

Alcoholic Intoxication↗
PubMed1998

Temporal architecture of violent incidents.

Five hundred five reports of violent incidents in British pubs and bars were studied by using logical pathway modeling to provide information on the processes underlying work-related violence. Logical pathway modeling is innovative in examining and mapping sequences in real incidents at a population level. The data reveal the most common pathway to be misbehavior by customers, intervention by staff (before any physically violent act), physical attack on staff, and injury to staff. The data also highlight the likelihood of further action after assailants have exited and identify stages in incidents at which most staff and customer injuries and damage to property occur. Results assist in the design of strategies to reduce the risk from future violence, particularly by training staff to recognize and to handle potentially violent situations and to maintain vigilance and security following problem incidents.

Accidents, Occupational↗
PubMed1998

Independent recovery of memory and language functioning during the Intracarotid Sodium Amytal Test.

Memory and language recovery during the Intracarotid Sodium Amytal Test (IAP) was investigated in 49 left-hemisphere-dominant patients with unilateral temporal epileptic seizure foci. Memory was assessed by presenting items (words, objects, and faces) immediately after injection, and testing for recognition memory 10 min after motoric recovery. To assess language the patients responded verbally to the same items during memory presentation. Memory for the individual items was found to be independent of their presentation order and language functioning was impaired only with the dominant-hemisphere injection, recovering during the presentation of the memory items. These results suggest that the encoding of material remains at a constant level throughout the initial active phase of the IAP, whereas language functioning recovers independently.

Adult↗
PubMed1998

Staphylococcus succinus sp. nov., isolated from Dominican amber.

Two bacterial isolates, designated AMG-D1T and AMG-D2, were recovered from 25-35-million-year-old Dominican amber. AMG-D1T and AMG-D2 biochemically most closely resemble Staphylococcus xylosus; they differ physiologically from other staphylococci. Fatty acid analysis and comparisons with extensive databases were unable to show relatedness to any specific taxon. Moreover, AMG-D1T and AMG-D2 contain tuberculostearic acid and meso-diaminopimelic acid, characteristic of the G + C-rich coryneform bacteria, as opposed to L-lysine characteristic of staphylococci. AMG-D1T and AMG-D2 have a G + C ratio of 35 mol%. Phylogenetic analysis with the 16S rRNA gene indicated that AMG-D1T and AMG-D2 were most closely related to Staphylococcus equorum, S. xylosus, Staphylococcus saprophyticus and other novobiocin-resistant staphylococci. Stringent DNA-DNA hybridization studies with AMG-D1T revealed similarities of 38% with S. equorum, 23% with S. xylosus and 6% with S. saprophyticus. The results indicate that AMG-D1T and AMG-D2 represent a novel species, which was named Staphylococcus succinus sp. nov. The type strain of the new species is AMG-D1 (ATCC 700337).

Amber↗
PubMed1998

Neuroimaging and spectroscopy in children with epileptic encephalopathies.

AIMS: To investigate the nature of the unifocal cortical abnormalities on FDG positron emission tomography (PET) in children with an epileptic encephalopathy but no focal abnormality on electroencephalogram or standard magnetic resonance imaging (MRI). METHODS: Repeat FDG PET, surface rendered high resolution MRI, and single voxel magnetic resonance proton spectroscopy of the areas of abnormal metabolism compared to the contralateral side in 11 children aged 2 to 12 years. Imaging was repeated after a median of 13 months. RESULTS: Visual analysis of repeat FDG PET revealed similar abnormalities in 10 of 11 children. Semiquantitative analysis revealed similar sited abnormalities in eight children. One child with ictal hypermetabolism initially had an inconsistent second scan. Magnetic resonance spectra in three children showed the N-acetyl-aspartate/choline ratio was lower in the hypometabolic focus than in the reciprocal area on the opposite side, in two children it was higher, and in one child it was equal. Surface rendered MRI was normal in seven of eight children, and showed temporal lobe asymmetry in one. CONCLUSION: In children with established epileptic encephalopathies most hypometabolic areas on FDG PET are stable over time. While focal neuronal loss is likely in these areas in some children, microdysplasias or other focal cortical dysplasias are probable in others.

Brain↗
PubMed1998

Interictal regional slow activity in temporal lobe epilepsy correlates with lateral temporal hypometabolism as imaged with 18FDG PET: neurophysiological and metabolic implications.

OBJECTIVES: The phenomenon of interictal regional slow activity (IRSA) in temporal lobe epilepsy and its relation with cerebral glucose metabolism, clinical data, MRI, and histopathological findings was studied. METHODS: Interictal 18F-fluorodeoxyglucose positron emission tomography (FDG PET) was performed under continuous scalp EEG monitoring in 28 patients with temporal lobe epilepsy not associated with intracranial foreign tissue lesions, all of whom subsequently underwent resective surgery. Regions of interest (ROIs) were drawn according to a standard template. IRSA was considered lateralised when showing a 4:1 or greater ratio of predominance on one side. RESULTS: Sixteen patients (57%) had lateralised IRSA which was always ipsilateral to the resection and of maximal amplitude over the temporal areas. Its presence was significantly related to the presence of hypometabolism in the lateral temporal neocortex (p=0.0009). Logistic regression of the asymmetry indices for all measured cerebral regions confirmed a strong association between IRSA and decreased metabolism of the posterior lateral temporal neocortex only (p=0.009). No significant relation could be shown between slow activity and age at onset, duration of the epilepsy, seizure frequency, and MRI evidence for hippocampal atrophy. Furthermore, IRSA was not specifically related to mesial temporal sclerosis or any other pathology. CONCLUSIONS: Interictal regional slowing in patients with temporal lobe epilepsy not associated with a mass lesion is topographically related to the epileptogenic area and therefore has a reliable lateralising, and possibly localising, value. Its presence is irrelevant to the severity or chronicity of the epilepsy as well as to lateral deactivation secondary to neuronal loss in the mesial temporal structures. Although slow EEG activity is generally considered as a non-specific sign of functional disturbance, interictal regional slowing in temporal lobe epilepsy should be conceptualised as a distinct electrographic phenomenon which is directly related to the epileptogenic abnormality. The strong correlation between interictal regional slowing and lateral temporal hypometabolism suggests in turn that the second may delineate a field of reduced neuronal inhibition which can receive interictal and ictal propagation.

Adolescent↗
PubMed1997

Central corneal thickness in normal, glaucomatous, and ocular hypertensive eyes.

OBJECTIVE: To determine the relationship between central corneal thickness (CCT) and applanation intraocular pressure (IOP) in normal, glaucomatous, and ocular hypertensive eyes. METHODS: One hundred nine subjects (184 eyes) were studied. Forty-eight patients (74 eyes) had glaucoma, 28 patients (51 eyes) had ocular hypertension, and 33 patients (59 eyes) were normal. Intraocular pressure as measured by applanation tonometry, refractive status, CCT, and axial length were measured for all subjects. RESULTS: The CCT (mean +/- SD) of eyes with ocular hypertension was significantly greater (0.606 +/- 0.041 mm) than that of glaucomatous eyes (0.554 +/- 0.022 mm) (P < .001) or of normal controls (0.561 +/- 0.026 mm) (P < .001). There was no significant difference in CCT between normal and glaucomatous eyes (P = .40). The axial length (mean +/- SD) of eyes with ocular hypertension (23.54 +/- 1.34 mm) was not different compared with glaucomatous eyes (23.93 +/- 0.96 mm) (P = .13) or normal eyes (23.62 +/- 1.21 mm) (P = .83). There was no significant difference between the axial length for glaucomatous eyes compared with normal eyes (P = .18). Those eyes with glaucoma being treated with topical dorzolamide hydrochloride had a significantly increased CCT (0.560 +/- 0.025 mm) compared with those eyes with glaucoma not being treated with dorzolamide (0.551 +/- 0.20 mm) (P = .02). CONCLUSIONS: The mean CCT is increased in eyes with ocular hypertension when compared with normal or glaucomatous eyes, which confirms the findings of other investigators. Increased CCT may give an artificially high IOP measurement by applanation tonometry. The CCT must be considered when developing a treatment approach for patients with ocular hypertension.

Aged↗
PubMed1997

Psychosocial factors predicting employee sickness absence during economic decline.

Psychosocial factors such as work characteristics, life events, social support, and personality were examined as predictors of the change in medically certified sickness absence observed during a period of severe economic decline. Longitudinal data, derived from self-reports and register-based information relating to 763 local government employees, were collected at 3 points during a 5-year period: before the economic decline, during the nadir of that decline, and immediately after the nadir. After the effects of prior absence and demographic and lifestyle variables had been partialed out, the results of multiple Poisson regression analyses showed that work characteristics play a major role in forthcoming sickness absences. Negative life events and the personality trait sense of coherence (in women) also predicted forthcoming absence rate. Social support did not relate to absences either in men or in women.

Adult↗
PubMed1997

Progressive facial hemiatrophy: MRI appearances.

The cranial CT and MRI appearances of a 14-year-old girl with Parry-Romberg syndrome and epilepsy are described. The findings are compared with the two published descriptions of MRI and CT in such patients. MRI appearances in our patient differ from those published and may be consistent with a vascular malformation. The one published report on the intracranial histopathology of a patient with Parry-Romberg syndrome and epilepsy states that a microscopic vascular malformation was found. We discuss the relationship between radiological and pathological findings. The possible aetiologies of Parry-Romberg syndrome (vascular malformation, immunological, trauma, sympathetic innervation, hereditary, slow virus) are discussed. We suggest that Parry-Romberg syndrome could be regarded as a neurocutaneous syndrome, a component of which includes intracerebral vascular dysplasia. In this and the other three cases of Parry-Romberg syndrome with epilepsy, the sensitivity of MRI in detecting intracranial lesions is demonstrated. Recommendations for imaging these patients are proposed.

Brain Diseases↗