Dose reduction of etanercept--can we treat more patients using a fixed budget?
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Antirheumatic Agents↗
Biomedical subjects
R Watts
Publications and source records attributed to R Watts.
Epidemiologic study of 203 sibling pairs with Parkinson's disease: the GenePD study.
OBJECTIVE: To examine patterns of familial aggregation and factors influencing onset age in a sample of siblings with PD. METHODS: Sibling pairs (n = 203) with PD were collected as part of the GenePD study. Standardized family history, medical history, and risk factor data were collected and analyzed. RESULTS: The mean age at onset was 61.4 years and did not differ according to sex, exposure to coffee, alcohol, or pesticides. Head trauma was associated with younger onset (p = 0.03) and multivitamin use with later onset (p = 0.007). Age at onset correlation between sibling pairs was significant (r = 0.56, p = 0.001) and was larger than the correlation in year of onset (r = 0.29). The mean difference in onset age between siblings was 8.7 years (range, 0 to 30 years). Female sex was associated with increased frequency of relatives with PD. The frequency of affected parents (7.0%) and siblings (5.1%) was increased when compared with frequency in spouses (2.0%). CONCLUSIONS: The greater similarity for age at onset than for year of onset in sibling pairs with PD, together with increased risk for biological relatives over spouses of cases, supports a genetic component for PD. Risk to siblings in this series is increased over that seen in random series of PD cases; however, patients in this sample have similar ages at onset and sex distribution as seen for PD generally. These analyses suggest that factors influencing penetrance are critical to the understanding of this disease.
Age of Onset↗
Recessed elliptical-centric view-ordering for contrast-enhanced 3D MR angiography of the carotid arteries.
Fast arterial-venous transit in the carotid arteries requires accurate, reliable timing of the acquisition to the bolus transit to maximize arterial signal and minimize venous artifacts. The rising edge of the bolus is not utilized in conventional elliptical-centric view-ordering because the critical k-space center must be acquired with full arterial enhancement. In this study, a recessed elliptical-centric view-ordering scheme is introduced in which the k-space center is acquired a few seconds following scan initiation. The recessed view-ordering is shown to be more robust to timing errors than the conventional scheme in a study of 37 patients.
Carotid Artery Diseases↗
k-Space weighted least-squares algorithm for accurate and fast motion extraction from magnetic resonance navigator echoes.
Navigator echoes provide an effective method to monitor physiological motion, allowing motion artifacts to be suppressed by modifying the data acquisition accordingly. The displacement can be measured directly from the navigator phase using an algorithm suggested by Ahn and Cho (IEEE Trans Med Imaging 1987;MI-6:32-36). Although computationally efficient, it is susceptible to noise, particularly contributions from points at the edges of k-space. A k-space weighted least-squares (kLS) algorithm is proposed which fits a straight line to the motion-induced phase shift. The linear fit is weighted strongly to high SNR points near the k-space center and only weakly to the poor SNR points at the edges of k-space. This algorithm was found to be as efficient as Ahn's algorithm but more robust against noise.
Algorithms↗
Optimization of view ordering for motion artifact suppression.
Motion artifacts in MRI may be reduced by optimized view ordering. Extensive simulations of view-ordering techniques were performed on high-resolution phantom images to determine the best strategy for distributing motion in k-space. Although not exhaustive, simulation results indicate that minimizing motion at the center of k-space is critical to overall image quality. For 2D imaging, using edge-center-edge view order and setting the readout direction parallel to the direction of the motion produces the sharpest point spread function and the lowest image energy error. For 3D imaging, using an edge-center-edge view order proves to be the optimum choice in general. Given these observations, several important issues regarding the measurement of motion effects are discussed.
Algorithms↗
Audit of a multidisciplinary approach to the care of children with unilateral and bilateral cleft lip and palate.
Cleft lip and palate affects the child in many ways, particularly appearance, dental arch relationships, growth of the face, and speech development. The key to successful care is management in a multidisciplinary team adhering to a well-designed protocol, and careful audit of results. We present the intermediate outcome audit of 15 patients with complete bilateral and unilateral cleft lip and palate whose condition was managed in a multidisciplinary team according to a strict protocol. We give the results observations of operations of a single surgeon's functional primary surgery over a 6-year period in terms of dental arch relationships, cephalometric analyses, aesthetic assessments, and speech analysis. The results show good early facial growth, with dental arch relationships appropriate for the age and group; we found only minor speech discrepancies, with no patients requiring pharyngoplasty. The results show the importance of multidisciplinary management, the value of keeping to sound surgical protocols, and functional techniques in cleft lip and palate surgery. Our study includes the neglected group of children who have bilateral cleft lip and palate, and it conforms to the style of pan-European projects.
Cephalometry↗
Contrast-enhanced peripheral MR angiography from the abdominal aorta to the pedal arteries: combined dynamic two-dimensional and bolus-chase three-dimensional acquisitions.
UNLABELLED: Wang Y, Winchester PA, Khilnani NM, et al. Contrast-enhanced peripheral MR angiography from the abdominal aorta to the pedal arteries: Combined dynamic two-dimensional and bolus-chase three-dimensional acquisitions. Invest Radiol 2001;36:170-177. RATIONALE AND OBJECTIVES: To obtain reliable contrast-enhanced peripheral MR angiography for imaging peripheral vascular disease from the abdominal aorta to the pedal arteries. METHODS: A protocol consisting of contrast-enhanced, dynamic two-dimensional (2D) acquisition at the feet and calf and bolus-chase three-dimensional (3D) acquisition from the abdominal aorta to the calf was developed and applied in patients with peripheral vascular disease. The performance of this integrated protocol was assessed in 89 consecutive patients. RESULTS: The bolus-chase 3D acquisition was of diagnostic quality in 100% of the acquisitions in the abdomen, 96% in the thigh, and 43% in the calf. The poor quality of the calf acquisitions was due to insufficient spatial resolution, poor arterial signal, and venous contamination. Diagnostic-quality images were obtained in 100% of the dynamic 2D acquisitions of the calf and 98% of the feet. CONCLUSIONS: The combined dynamic 2D and bolus-chase 3D contrast-enhanced MR angiography technique provides diagnostic images of the entire lower extremity.
Adult↗
Coronary MR angiography: selection of acquisition window of minimal cardiac motion with electrocardiography-triggered navigator cardiac motion prescanning--initial results.
The authors developed an electrocardiography-triggered M-mode navigator-echo technique to help monitor cardiac motion and identify the period of minimal cardiac motion in the cardiac cycle. Coronary magnetic resonance angiography was performed in eight healthy adult volunteers and one patient with heart disease. To minimize cardiac motion effects, trigger delays were estimated with the navigator-echo technique and two empirical formulas. The quality of images obtained with the different delay times was compared for clarity of depiction of the coronary arteries. Image quality was best with the delay calculated with the navigator-echo technique.
Adult↗
Anatomically tailored k-Space sampling for bolus-chase three-dimensional MR digital subtraction angiography.
The purpose of this study was to evaluate a variable k-space sampling method for bolus-chase three-dimensional magnetic resonance digital subtraction angiography in the arterial system from the abdomen to the calf. Imaging time was minimized by tailoring the acquisition according to the vascular anatomy of the station. For images obtained in 30 patients, results with the modified protocol were compared to those with the previously published protocol. For all stations, significant improvement (P <.001) was found with the modified protocol.
Adult↗
Induction of anti-DNA antibodies: commentary on article by Satake et al.
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Animals↗
Evidence for accelerated desensitisation of 5-HT(2C) receptors following combined treatment with fluoxetine and the 5-HT(1A) receptor antagonist, WAY 100,635, in the rat.
Both pre-clinical and clinical studies suggest that additional treatment with 5-HT(1A) receptor antagonists may accelerate the antidepressant efficacy/onset of selective serotonin re-uptake inhibitors (SSRIs). Given that chronic SSRI treatment has been shown to desensitise 5-HT(2C) receptor mediated responses, we have used the rat social interaction test to determine if combined treatment with WAY 100,635, a selective 5-HT(1A) receptor antagonist, will accelerate this effect. In pairs of unfamiliar rats, acute administration of the 5-HT(2C) receptor agonist m-chlorophenylpiperazine (mCPP) or fluoxetine decreased the time spent in social interaction, responses which were reversed by the 5-HT(2C/2B) receptor antagonists SB 200646A and SB 221284. Similar reductions in social interaction were observed in rats treated with fluoxetine (10 mg/kg, i.p. daily) for 4, 7 and 14 days but was no longer apparent after 28 days of treatment. In contrast, only 7 days of combined treatment with WAY 100,635 (1 mg/kg/s.c./day) and fluoxetine were needed to reverse this response. The decrease in social interaction induced by an acute challenge of mCPP (1 mg/kg, i. p.) was also reduced after 6 days co-treatment with WAY 100,635 and fluoxetine. Thus, WAY 100,635 accelerates SSRI-induced desensitisation of 5-HT(2C) receptors, suggesting that this response might contribute towards the therapeutic effects of SSRIs in man.
Animals↗
Candesartan cilexetil is not associated with cough in hypertensive patients with enalapril-induced cough. Multicentre Cough Study Group.
The aim of this study was to evaluate the occurrence of dry cough during treatment with candesartan cilexetil, enalapril, or placebo in patients with hypertension and a history of angiotensin converting enzyme (ACE)-inhibitor-related cough. Patients with confirmed cough during an enalapril (10 mg) challenge period, followed by no cough during a placebo dechallenge period were randomized to 8 weeks of double-blind treatment with candesartan cilexetil (8 mg) (n = 62), enalapril (10 mg) (n = 66), or placebo (n = 26). Incidence and severity of dry cough was evaluated by the symptom assessment questionnaire, frequency of dry cough by a visual analog scale, and the possible impact on quality of life by the minor symptom evaluation (MSE) profile. The percentage of patients with cough was significantly lower with candesartan cilexetil (35.5%) than with enalapril (68.2%, P < .001), and did not differ between candesartan cilexetil and placebo (26.9%, P > .20). Patients coughed less frequently and with less severe cough with candesartan cilexetil than with enalapril, and similarly with candesartan cilexetil and placebo. Changes in the MSE profile were minor, although candesartan cilexetil had better scores for contentment than placebo (P = .03), and also tended to be associated with better sleep than enalapril (P = .08). In hypertensive patients with ACE-inhibitor-induced cough, the incidence, frequency, and severity of dry cough was significantly lower with candesartan cilexetil than with enalapril, and no different from that found with placebo.
Adult↗
Breath-hold three-dimensional contrast-enhanced coronary MR angiography: motion-matched k-space sampling for reducing cardiac motion effects.
A view order that matches k-space sampling to cardiac motion within the acquisition window was developed for breath-hold three-dimensional contrast material-enhanced coronary magnetic resonance angiography. In vivo experiments in seven volunteers demonstrated that blurring was substantially reduced with this motion-matched view order as compared with the standard centric view order. Coronary arteries were well delineated.
Adult↗
Magma flow instability and cyclic activity at soufriere hills volcano, montserrat, british west indies
Dome growth at the Soufriere Hills volcano (1996 to 1998) was frequently accompanied by repetitive cycles of earthquakes, ground deformation, degassing, and explosive eruptions. The cycles reflected unsteady conduit flow of volatile-charged magma resulting from gas exsolution, rheological stiffening, and pressurization. The cycles, over hours to days, initiated when degassed stiff magma retarded flow in the upper conduit. Conduit pressure built with gas exsolution, causing shallow seismicity and edifice inflation. Magma and gas were then expelled and the edifice deflated. The repeat time-scale is controlled by magma ascent rates, degassing, and microlite crystallization kinetics. Cyclic behavior allows short-term forecasting of timing, and of eruption style related to explosivity potential.
Journal Article↗
Speech outcome in children with cleft palate: aerophonoscope assessment of nasal emission.
The quality of speech is an important outcome measure of the success of primary surgery for clefts of the palate. A competent velopharyngeal mechanism is essential for normal speech, and disorders of resonance and nasal airflow are significant manifestations of velopharyngeal dysfunction in cleft palate subjects. The aim of this study was to determine the level of nasal emission during speech in patients with functionally repaired clefts of the palate and compare this with age and sex-matched controls. Forty-four children between the ages of 3 and 9 years were assessed for nasal emission using an Aerophonoscope. All these patients had primary functional surgery carried out at this unit by the same surgeon, and fell into three groups; complete bilateral, complete unilateral and soft palate clefts. Nasal breathing, blowing and groups of vowels and voiceless pressure consonants were assessed. There was no nasal emission in close to, or over, 90% of the patients for these parameters. The results indicate that a highly significant percentage of children with functionally repaired clefts of the palate have normal velopharyngeal function and speech, without inappropriate nasal emission. The Aerophonoscope provides an accurate, reliable and user-friendly diagnostic aid, and indeed therapeutic adjunct, to speech management in cleft palate patients.
Child↗
Target genes and regulatory domains of the GAMYB transcriptional activator in cereal aleurone.
GAMYB is an MYB transcription factor which is expressed in cereal aleurone cells in response to gibberellin (GA). HvGAMYB binds to the TAACAAA box of a high-pl alpha-amylase gene promoter and transcriptionally activates its expression. In this study, we examined the role of HvGAMYB in activating expression of other GA-regulated genes encoding hydrolytic enzymes. In transient expression experiments, HvGAMYB transactivated expression of reporter genes fused to a low-pl alpha-amylase gene promoter, an EII (1-3, 1-4)-beta-glucanase gene promoter and a cathepsin B-like protease promoter. HvGAMYB DNA binding specificity was determined using a PCR-based random site selection using HvGAMYB fusion protein isolated from E. coli. The deduced consensus closely resembled gibberellin response elements in alpha-amylase promoters. Functional analysis of HvGAMYB by transient expression of C terminal HvGAMYB deletions in barley aleurone cells identified two transcriptional activation domains (TADs) which function in transcriptional regulation of both high- and low-pl alpha-amylase promoters. The same TADs were identified using a heterologous yeast expression system. Together, these results indicate that HvGAMYB has two TADs. These domains are C-terminal to its DNA-binding domain.
Base Sequence↗
Psychosocial outcome risk indicator: predicting psychosocial outcome following traumatic brain injury.
This study examines the outcome of 29 individuals with traumatic brain injury (TBI) and 23 of their respective significant others, 12 months after discharge from inpatient rehabilitation services, as a means of determining the validity of a measure developed to predict psychosocial outcome. This measure consists of 18 questions that examine 12 factors and requires the rater to make a judgement about the likely impact each factor would have on the individual with TBI and significant other. Results indicate that the social work raters accurately predicted outcome according to the factors contained in the measure. Scores on the measure at discharge were also found to be associated with general psychological distress, anxiety and insomnia, depression, family functioning, and the problems related to emotion and behaviour. Although the sample size was small, there is an indication that the devised measure is useful in predicting outcome and so has clinical value in identifying adults at greatest risk of poor psychosocial outcome after a traumatic brain injury.
Adolescent↗
An unusual cause of blindness in Wegener's granulomatosis.
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Blindness↗