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Biomedical subjects

C Watson

Publications and source records attributed to C Watson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Structural analysis of the binding modes of minor groove ligands comprised of disubstituted benzenes.

Two-dimensional homonuclear NMR was used to characterize synthetic DNA minor groove-binding ligands in complexes with oligonucleotides containing three different A-T binding sites. The three ligands studied have a C(2) axis of symmetry and have the same general structural motif of a central para-substituted benzene ring flanked by two meta-substituted rings, giving the molecules a crescent shape. As with other ligands of this shape, specificity seems to arise from a tight fit in the narrow minor groove of the preferred A-T-rich sequences. We found that these ligands slide between binding subsites, behavior attributed to the fact that all of the amide protons in the ligand backbone cannot hydrogen bond to the minor groove simultaneously.

AT Rich Sequence↗
PubMed2001

Regulation of expression of IL-4 alleles: analysis using a chimeric GFP/IL-4 gene.

CD4 cells from mice heterozygous for an IL-4 and a GFP/IL-4 gene frequently express a single allele. Analysis of IL-4 or GFP production by cells from recently primed Th2 cells indicates that essentially all are competent to transcribe either allele but have a low probability of doing so. By contrast, long-term Th2 clones show distinct and heritable ratios in the proportion of cells that express IL-4 or GFP. We conclude that in the course of Th2 priming an early efficient event renders both alleles capable of being inefficiently transcribed; a second, less frequent event occurs that renders one allele more competent, accounting for the differential expression of IL-4 and GFP in different clones.

Alleles↗
PubMed2001

Disrupting Il13 impairs production of IL-4 specified by the linked allele.

Interleukin 13-deficient (IL-13-/-) mice express a defect in priming for IL-4 production that is not corrected by adding IL-13 to the priming culture. This is partly accounted for by the consumption of IL-4 without endogenous replacement during culture of IL-13-/- CD4+ T cells. We examined cells from mice in which disrupted Il13 was linked to wild-type Il4 on one chromosome and wild-type Il13 was linked to a "knocked-in" green fluorescent protein (Gfp) gene in the Il4 locus. Our results show that the deficit in IL-4 production was due, at least in part, to a cis effect, in which disrupted Il13 diminished IL-4 production from the linked Il4 gene.

Alleles↗
PubMed2001

Naratriptan as short-term prophylaxis of menstrually associated migraine: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To determine the efficacy of naratriptan 1-mg and 2.5-mg tablets twice daily compared with placebo as short-term prophylaxis of menstrually associated migraine. BACKGROUND: Approximately 60% of women with migraine report headaches associated with their menstrual cycles. Results from an open-label study suggest that short-term administration of sumatriptan is useful in the prophylaxis of menstrually associated migraine. METHODS: A randomized, double-blind, three-arm, parallel-group, placebo-controlled study was conducted in women aged 18 years or older with a history of migraine with or without aura, as defined by the International Headache Society, of at least 6 months. Two dose strengths of naratriptan (1 mg, 2.5 mg) or identical-appearing placebo tablets (1:1:1) were administered twice daily for 5 days starting 2 days prior to the expected onset of menses across four perimenstrual periods. End points included the number of menstrually associated migraines, total migraine days, peak headache severity, lost work/activity time, migraine-related quality of life, and incidence of adverse events. RESULTS: Overall, the intent-to-treat population comprised 206 women (naratriptan 1 mg, n = 70; naratriptan 2.5 mg, n = 70, and placebo, n = 66); 171 women treated four perimenstrual periods. Significantly more perimenstrual periods per subject treated with naratriptan, 1 mg, were headache-free compared with placebo (50% versus 25%, P =.003). Naratriptan, 1 mg, significantly reduced the number of menstrually associated migraines (2.0 versus 4.0, P <.05) and menstrually associated migraine days (4.2 versus 7.0, P <.01) compared with placebo. More patients treated with naratriptan, 1 mg, were headache-free across all treated perimenstrual periods compared with placebo (23% versus 8%). No difference in headache severity was observed in breakthrough headaches. The incidence and severity of adverse events was similar across treatment groups. Naratriptan, 2.5 mg, was not statistically superior to placebo for any measure. CONCLUSIONS: Naratriptan, 1 mg, with tolerability similar to placebo, is an effective, short-term, prophylactic treatment for menstrually associated migraine.

Adult↗
PubMed2001

Peripheral WBC count and serum prolactin level in various seizure types and nonepileptic events.

PURPOSE: To analyze effects of different types of seizures and nonepileptic events as well as effects of seizure duration and lapse between the time of seizure and blood collection on serum prolactin level and peripheral white blood cell (WBC) count. METHODS: We prospectively collected blood samples from all patients admitted to our Epilepsy Monitoring Unit at baseline and after an event. Blood samples were analyzed, and serum prolactin level and WBC count were determined. Statistical analyses were performed to evaluate the relation of each type of seizure, its duration, and time lapse between a seizure and collection of blood sample to the serum prolactin level and peripheral WBC count. RESULTS: Serum prolactin level increases above twice the level at baseline after a complex partial seizure or a generalized seizure. Peripheral WBC count is elevated above the upper limit of normal in about one third of cases after a generalized seizure. In generalized seizures, the length of a seizure is positively associated, whereas the lapse time between the seizure onset and blood draw is negatively correlated with the increase in WBC count. Thus the longer the seizure and quicker the blood draw, the higher the WBC count. CONCLUSIONS: We conclude that complex partial or generalized seizures are associated with an increase in serum prolactin level. Peripheral WBC count increases significantly after a generalized seizure and is probably transient in nature.

Electroencephalography↗
PubMed2001

High-titer screening PCR: a successful strategy for reducing the parvovirus B19 load in plasma pools for fractionation.

BACKGROUND: Human parvovirus B19 (B19) is regarded as a potential risk factor for certain patient populations receiving plasma components. STUDY DESIGN AND METHODS: The prevalence of B19 was determined in a limited plasma donor population. Conditions for high-titer screening PCR were designed to allow the removal of plasma donations in the acute phase of infection with virus loads >or=10(7) genome equivalents per milliliter before manufacturing. Antithrombin III lots originating from screened plasma were compared to lots originating from untested plasma with respect to their B19 DNA load by a sensitive PCR assay. RESULTS: B19 was shown to have a prevalence of about 1 per 800 plasma donations. Only a minority (1/8000) of occurrences were in the acute phase of infection. Removing plasma units with high virus load as determined by high-titer screening PCR significantly decreased peak virus loads of plasma pools for fractionation. Together with a virus-removal capacity of 10.4 log(10) of the manufacturing process, this screening resulted in a final antithrombin III product that was nonreactive for B19 on PCR. CONCLUSION: Combining the strategy of high-titer screening PCR with the virus reduction capacity of the manufacturing process considerably increased the margin of B19 virus safety of antithrombin III. This strategy should have positive impact on other plasma components as well.

Antithrombin III↗
PubMed2001

Improved quality of life among patients with symptomatic carotid artery disease undergoing carotid endarterectomy.

BACKGROUND: Few studies have examined how carotid endarterectomy affects patients' view of their quality of life. METHODS: Patients undergoing carotid endarterectomy from January 1996 to March 1997 at the John Radcliffe Hospital completed the United Kingdom Short Form 36 (SF-36) Health Survey Questionnaire before undergoing the procedure and again at 3 months afterward. Scores were compared with population normal values. RESULTS: In 50 patients with symptomatic carotid artery disease, there was significant improvement in the SF-36 overall "change in health" score after the procedure compared with beforehand (61.0 +/- 3.7 vs 44.5 +/- 3.4, P =.003, Wilcoxon signed rank test). There were, however, no statistically significant differences in the group's mean SF-36 subscores after operation compared with before the procedure. The physical subscores were below age-adjusted healthy population means but similar to those for chronically ill patients (physical function subscore P =.015 vs normal, P =.89 vs ill; role limitation-physical subscore P =.007 vs normal, P =.89 vs ill). Patients with postoperative complications did not have an improved change in health score (-12.5 vs 22.0, P =.03, Mann-Whitney U test). There was no effect on change in health score because of other risk factors or in patients with contralateral carotid artery occlusion or a history of preoperative stroke. CONCLUSIONS: Patients with symptomatic carotid artery disease undergoing an uncomplicated carotid endarterectomy perceive improved quality of life and overall health. There is no perception of worsened pain, energy, or physical or mental function after the procedure. These results confirm that patients believe that performance of carotid endarterectomy improves their overall health, supporting the surgical approach to carotid artery disease.

Aged↗
PubMed2001

Reduction of chronic aggressive behaviour 10 years after brain injury.

This study demonstrates the successful management of aggressive behaviour with a client 10 years post-injury in a small, residential neurorehabilitation unit. The case presented is unusual for two main reasons. First, it proved possible to significantly modify previously chronic challenging behaviour many years after brain injury had been sustained. Secondly, the rehabilitation environment in which treatment was conducted did not comprise a highly specialized neurobehavioural service, Instead, staff were specifically trained regarding the administration of the treatment programme, which was based on principles derived from behaviour modification and applied neuropsychology. Specific interventions used included those of differential reinforcement and graduated increase of expectations. Recordings made over the course of 85 weeks demonstrate a significant decrease in the frequency and severity of aggression. Successful inhibition of challenging behaviour attained a level which facilitated transfer of the client to a non-institutionalized community home. Reasons underlying the success of the intervention, and the limitations inherent in attempting to manage aggression within neurorehabilitation environments will be discussed.

Adult↗
PubMed2001

Death from multi-resistant shigellosis in Fiji Islands.

Death from Shigellosis is rare in developed countries, however it causes over a million deaths in developing countries worldwide annually. Death from shigellosis is rare in Fiji. However, the global problem of emerging multidrug resistance raises some issues about the management of Shigellosis in this country. Within Fiji, Shigella is a notifiable disease. The Fiji Ministry of Health recorded 68 cases of Shigella in 1996, 173 cases in 1997 and 334 cases in 1998 (no data available for 1999). There was only one recorded death during this time--in 1998. Resistance to chloramphenicol occurred in 82% of cases. Shigella flexneri in Fiji remains sensitive to cephalothin and cefaclor. The current antibiotic guidelines in Fiji, recommend that antibiotics be used only for cases of moderate and severe dysentery. Shigellosis was suspected soon after presentation however the patient was unable to take oral antibiotics and was treated with intravenous antibiotics (chloramphenicol and ampicillin), which were ineffective due to resistance of the organism. The current antibiotic guidelines for severe dysentery recommend chloramphenicol or nalidixic acid--the later not available in Fiji. However the only intravenous drugs that retain their sensitivity to Shigella-ceftriaxone and cephalothin, are expensive ($F 45.00 per vial of ceftriaxone) and these are only available in large regional hospitals.

Adult↗
PubMed2000

Electroclinical correlates of flumazenil and fluorodeoxyglucose PET abnormalities in lesional epilepsy.

OBJECTIVE: To analyze the clinical utility of [11C]flumazenil (FMZ) PET to detect perilesional and remote cortical areas of abnormal benzodiazepine receptor binding in relation to MRI, 2-deoxy-2-[18F]fluoro-d-glucose (FDG) PET, and electrocorticographic (ECoG) findings as well as clinical characteristics of the epilepsy in epileptic patients with brain lesion. BACKGROUND: The success of resective surgery in patients with medically intractable epilepsy and brain lesion depends not only on removal of the lesion itself but also on the reliable presurgical delineation of the epileptic cortex that commonly extends beyond it. PET could provide a noninvasive identification of such epileptogenic areas. METHODS: Seventeen patients underwent high resolution MRI, FDG and FMZ PET, and presurgical EEG evaluation, including chronic intracranial ECoG monitoring or intraoperative ECoG. Regional cortical FDG/FMZ PET abnormalities were defined on partial volume-corrected PET images using an objective method based on a semiautomated definition of areas with abnormal asymmetry. Structural lesions were defined on coregistered MRI. The marked PET abnormalities visualized on three-dimensional cortical surface were compared with each other, to the extent of MRI-defined lesion, as well as to ECoG findings. RESULTS: The mean surface extent of FMZ PET abnormalities was significantly larger than the corresponding structural lesions, but it was significantly smaller than areas of glucose hypometabolism. The size of perilesional FDG PET abnormalities showed a correlation with the lifetime number of seizures (r = 0.93, p = 0.001). The extent of perilesional FMZ PET abnormalities was independent of the seizure number and showed an excellent correspondence with spiking cortex, the resection of which resulted in seizure-free outcome in all but one operated patient. Remote FMZ PET abnormalities (n = 6) were associated with early age at seizure onset (p = 0.048) and appeared in ipsilateral synaptically connected regions from the lesion area. CONCLUSIONS: Three-dimensional surface-rendered FMZ PET is able to delineate perilesional epileptic cortex, and it may be especially useful to localize such areas in patients with extensive perilesional glucose hypometabolism associated with a large number of seizures. Remote FMZ PET abnormalities in patients with early onset and long duration of epilepsy might represent secondary epileptogenesis, but this requires further study.

Adolescent↗
PubMed2000

Multimodality imaging for improved detection of epileptogenic foci in tuberous sclerosis complex.

OBJECTIVE: Using interictal alpha-[11C]methyl-l-tryptophan ([11C]AMT) PET scan, the authors have undertaken a quantitative analysis of all tubers visible on MRI or 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) PET, to determine the relationship between [11C]AMT uptake and epileptic activity on EEG. BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder, often associated with cortical tubers and intractable epilepsy. The authors have shown previously that [11C]AMT PET scans show high tracer uptake in some epileptogenic tubers and low uptake in the remaining tubers. METHODS: Eighteen children, age 7 months to 16 years, were studied. Patients underwent video-EEG monitoring, PET scans of [11C]AMT and [18F]FDG, and T2-weighted or fluid-attenuated inversion recovery (FLAIR) MRI. [11C]AMT uptake values were measured in 258 cortical tubers delineated with coregistered MRI or [18F]FDG scans. Uptake ratios were calculated between the [11C]AMT uptake in tubers and those for normal cortex (tuber/normal cortex). Using the region of epileptiform activity, the authors performed receiver operator characteristics (ROC) analysis and determined the optimal uptake ratio for detecting presumed epileptogenic tubers. RESULTS: Tuber uptake ratios ranged from 0.6 to 2.0. Tuber uptake ratios in the epileptic lobes were higher than those in the nonepileptic lobes (p < 0.0001). All 15 patients with focal seizure activity showed one or more lesions with uptake ratio above 0.98 in the epileptic lobe. ROC analysis showed that a tuber uptake ratio of 0.98 resulted in a specificity of 0.91. CONCLUSIONS: Cortical tubers with [11C]AMT uptake greater than or equal to normal cortex are significantly related to epileptiform activity in that lobe. Together, interictal [11C]AMT PET and FLAIR MRI improve the detection of potentially epileptogenic tubers in patients with TSC being evaluated for epilepsy surgery.

Adolescent↗
PubMed2000

Selective omission of the donor cross-match before renal transplantation: efficacy, safety and effects on cold storage time.

BACKGROUND: A donor lymphocyte cross-match (XM) test performed before renal transplantation is considered mandatory but may delay the transplant and increase the cold storage time. With careful documentation of sensitizing events and with knowledge of previous antibody screening results, it is often possible to predict the XM result for a given donor HLA mismatch. In this study, a policy was adopted of omitting the pretransplant XM in patients in whom a negative result was predicted with absolute confidence. METHODS: Recipients were selected for cadaveric donor kidney transplantation using a computer algorithm based on HLA match, sensitization status, time on the waiting list and donor and recipient age. The immediate pretransplant cross-match test was omitted in non-sensitized recipients and in sensitized recipients where antibody specificities were precisely defined and not against donor HLA. RESULTS: From October 1997 to May 1999, 53 of 96 (55%) consecutive cadaveric kidney donor transplants were performed without a pretransplant XM. In all cases, a negative donor HLA-specific antibody XM was confirmed after transplantation. Omission of the pre-transplant XM was associated with a significant reduction in cold ischemic time (15.0 hr vs. 18.2 hr, P=0.01) and a reduced incidence of delayed graft function (13% vs. 33%, P=0.03). However, there was no difference in transplant outcome at 1 year. CONCLUSION: Rigorous attention to priming events together with careful antibody screening allows the pre-transplant XM test to be safely omitted in approximately half the patients awaiting renal transplantation. This policy allows a modest reduction in cold ischemia time, but it remains to be seen whether this is of clinical benefit.

Adult↗
PubMed2000

Intracranial EEG versus flumazenil and glucose PET in children with extratemporal lobe epilepsy.

OBJECTIVE: To compare abnormalities determined in 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and [11C]flumazenil (FMZ) PET images with intracranial EEG data in patients with extratemporal lobe epilepsy. BACKGROUND: Although PET studies with FDG and FMZ are being used clinically to localize epileptogenic regions in patients with refractory epilepsy, the electrophysiologic significance of the identified PET abnormalities remains poorly understood. METHODS: We studied 10 patients, mostly children (4 boys, 6 girls, aged 2 to 19 years; mean age, 11 years), who underwent FDG and FMZ PET scans, intracranial EEG monitoring, and cortical resection for intractable epilepsy. EEG electrode positions relative to the brain surface were determined from MRI image volumes. Cortical areas of abnormal glucose metabolism or FMZ binding were determined objectively based on asymmetry measures derived from homotopic cortical areas at three asymmetry thresholds. PET data were then coregistered with the MRI and overlaid on the MRI surface. A receiver operating characteristics (ROC) analysis was performed to determine the specificity and sensitivity of PET-defined abnormalities against the gold standard of intracranial EEG data. RESULTS: FMZ PET detected at least part of the seizure onset zone in all subjects, whereas FDG PET failed to detect the seizure onset region in two of 10 patients. The area under the ROC curves was higher for FMZ than FDG PET for both seizure onset (p = 0.01) and frequent interictal spiking (p = 0.04). Both FMZ and FDG PET showed poor performance for detection of rapid seizure spread (area under the ROC curve not significantly different from 0.5). CONCLUSIONS: [11C]flumazenil (FMZ) PET is significantly more sensitive than 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET for the detection of cortical regions of seizure onset and frequent spiking in patients with extratemporal lobe epilepsy, whereas both FDG and FMZ PET show low sensitivity in the detection of cortical areas of rapid seizure spread. The application of PET, in particular FMZ PET, in guiding subdural electrode placement in refractory extratemporal lobe epilepsy will enhance coverage of the epileptogenic zone.

Adolescent↗
PubMed2000

Is ictal recording mandatory in temporal lobe epilepsy? Not when the interictal electroencephalogram and hippocampal atrophy coincide.

OBJECTIVE: To investigate the concordance between scalp electroencephalogram (EEG) lateralization and side of hippocampal atrophy in patients with temporal lobe epilepsy (TLE). METHODS: We studied 184 consecutive patients with TLE without lesions other than those compatible with mesial temporal sclerosis. In this study, we studied specifically hippocampal atrophy and the results of scalp EEG investigation. Patients were classified according to the localization of interictal epileptiform discharges as unilateral, bilateral asymmetric, and bilateral symmetric. The EEG seizure onsets were also classified separately as unilateral, bilateral asymmetric, and bilateral symmetric. The hippocampal atrophy was determined by volumetric measurements using high-resolution magnetic resonance imaging (MRIVol). RESULTS: Only 3% of patients had discordance between the ictal and interictal EEG lateralizations; however, none of these had unilateral interictal EEG abnormalities. Interictal EEGs were considered unilateral in 62.0% of patients, bilateral asymmetric in 31.5%, and bilateral symmetric in 6.5%. Ictal EEGs were considered unilateral in 63.5% of patients, bilateral asymmetric in 30.0%, and bilateral symmetric in 6.5%. The MRIVol showed unilateral hippocampal atrophy in 60.9% of patients, bilateral asymmetric hippocampal atrophy in 19.0%, symmetric hippocampal atrophy in 3.8%, and normal volumes in 16.3%. There was a significant concordance between MRIVol lateralization and both interictal and ictal EEG lateralization (P<.001). All patients with unilateral hippocampal atrophy had concordant interictal and ictal EEG lateralization. Six (18.2%) of the 33 patients with bilateral asymmetric hippocampal atrophy had MRI lateralization discordant with EEG lateralization. CONCLUSIONS: We found a strong concordance between EEG and MRIVol lateralization in patients with TLE. Unilateral hippocampal atrophy predicted ipsilateral interictal epileptiform abnormalities and ipsilateral seizure onsets with no false lateralization. Previous studies in addition to the present series support that a concordant outpatient EEG evaluation in patients with TLE and unilateral hippocampal atrophy would obviate the need for inpatient EEG monitoring.

Adult↗
PubMed2000

Effect of motor tasks on the cortical topography of the human masseter muscle.

Non-invasive magnetic stimulation of the brain was earlier used to reveal the corticomotor representation of the human masseter muscle but it is unclear how motor tasks affect this map. An experimental approach incorporating transcranial magnetic stimulation of verified locations on the scalp, surface electromyography, and controlled muscle facilitation was used to disclose the corticomotor output map of the masseter during three isometric tooth-contact tasks, viz., tooth clenching in the intercuspal position, biting on the left molar teeth, and biting on the incisors. Map area was significantly different for all tasks, and map height and volume were also different for biting on the incisor teeth (p<0.05). There was evidence of task-related modulation of corticobulbar activity that appeared to be mainly of corticomotoneuronal origin, although the role of differential, task-associated peripheral afferent input from orofacial receptors could not be discounted.

Adult↗