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Biomedical subjects

Alan Jackson

Publications and source records attributed to Alan Jackson.

At least 37 records · Page 2Linked to original sources
PubMed2004

Influence of personal characteristics of individual women on sensitivity and specificity of mammography in the Million Women Study: cohort study.

OBJECTIVES: To examine how lifestyle, hormonal, and other factors influence the sensitivity and specificity of mammography. METHODS: Women recruited into the Million Women Study completed a questionnaire about various personal factors before routine mammographic screening. A sample of 122,355 women aged 50-64 years were followed for outcome of screening and incident breast cancer in the next 12 months. Sensitivity and specificity were calculated by using standard definitions, with adjustment for potential confounding factors. RESULTS: Breast cancer was diagnosed in 726 (0.6%) women, 629 in screen positive and 97 in screen negative women; 3885 (3.2%) were screen positive but had no subsequent diagnosis of breast cancer. Overall sensitivity was 86.6% and specificity was 96.8%. Three factors had an adverse effect on both measures: use of hormone replacement therapy (sensitivity: 83.0% (95% confidence interval 77.4% to 87.6%), 84.7% (73.9% to 91.6%), and 92.1% (87.6% to 95.0%); specificity: 96.8% (96.6% to 97.0%), 97.8% (97.5% to 98.0%), and 98.1% (98.0% to 98.2%), respectively, for current, past, and never use); previous breast surgery v no previous breast surgery (sensitivity: 83.5% (75.7% to 89.1%) v 89.4% (86.5% to 91.8%); specificity: 96.2% (95.8% to 96.5%) v 97.4% (97.3% to 97.5%), respectively); and body mass index < 25 v > or = 25 (sensitivity: 85.7% (81.2% to 89.3%) v 91.0% (87.5% to 93.6%); specificity: 97.2% (97.0% to 97.3%) v 97.4% (97.3% to 97.6%), respectively). Neither sensitivity nor specificity varied significantly according to age, family history of breast cancer, parity, past oral contraceptive use, tubal ligation, physical activity, smoking, or alcohol consumption. CONCLUSIONS: The efficiency, and possibly the effectiveness, of mammographic screening is lower in users of hormone replacement therapy, in women with previous breast surgery, and in thin women compared with other women.

Body Mass Index↗
PubMed2004

Abnormalities on magnetic resonance imaging seen acutely following mild traumatic brain injury: correlation with neuropsychological tests and delayed recovery.

Mild traumatic brain injury (MTBI) is a common reason for hospital attendance and is associated with significant delayed morbidity. We studied a series of 80 persons with MTBI. Magnetic resonance imaging (MRI) and neuropsychological testing were used in the acute phase and a questionnaire for post-concussion syndrome (PCS) and return to work status at 6 months. In 26 subjects abnormalities were seen on MRI, of which 5 were definitely traumatic. There was weak correlation with abnormal neuropsychological tests for attention in the acute period. There was no significant correlation with a questionnaire for PCS and return to work status. Although non-specific abnormalities are frequently seen, standard MRI techniques are not helpful in identifying patients with MTBI who are likely to have delayed recovery.

Adult↗
PubMed2004

Functional contribution of medial premotor cortex to visuo-spatial transformation in humans.

This paper examines the functional contribution of medial premotor cortex, the supplementary motor area (SMA), to visuo-spatial transformation. Previous studies have found evidence of activation in SMA using 'mental rotation' tasks in which subjects make mirror-image judgements about simultaneously presented depth rotated novel forms. This manipulation induces potential confounds in the cognitive demands of the task in addition to spatial normalization processes. We clarify the role of SMA in visuo-spatial normalization using functional magnetic resonance imaging with a sequential mirror-image judgement task involving 2D image-plane rotated forms. The results show preferential activation of pre-SMA, as well as the ventrolateral prefrontal and parietal cortex during the visuo-spatial transformation of mirror-image stimuli.

Adult↗
PubMed2004

A comparison of Ktrans measurements obtained with conventional and first pass pharmacokinetic models in human gliomas.

PURPOSE: To compare in a group of patients with cerebral gliomas the estimates of Ktrans between a conventionally established pharmacokinetic model and a recently developed first pass method. MATERIALS AND METHODS: Glioma patients (23) were studied using T1-weighted dynamic contrast-enhanced magnetic resonance imaging (MRI), and two alternative pharmacokinetic models were used for analysis to derive the volume transfer constant Ktrans. These were a modified version of the established model (yielding KTK) and a recently published method based on first pass leakage profile (FP) of contrast bolus (yielding Kfp). RESULTS: We found a strong correlation between intra-tumoral median KTK and Kfp (rho = 0.650, P < 0.01), but the values from the conventional model were consistently and significantly higher (mean of inter-tumoral Kfp and KTK medians were 0.018 minute(-1) and 0.284 minute(-1), respectively, P < 0.001). The spatial distribution of KTK and Kfp showed poor correlation in the presence of large vascular structures and good correlation elsewhere. CONCLUSION: KTK and Kfp produce similar biologic information within voxels not dominated by vascular tissue. The FP method avoids erroneous overestimation of Ktrans in areas of significant intravascular contrast. Findings are in keeping with the predictions of previous mathematical simulations.

Adult↗
PubMed2004

Comparative study of methods for determining vascular permeability and blood volume in human gliomas.

PURPOSE: To characterize human gliomas using T1-weighted dynamic contrast-enhanced MRI (DCE-MRI), and directly compare three pharmacokinetic analysis techniques: a conventional established technique and two novel techniques that aim to reduce erroneous overestimation of the volume transfer constant between plasma and the extravascular extracellular space (EES) (Ktrans) in areas of high blood volume. MATERIALS AND METHODS: Eighteen patients with high-grade gliomas underwent DCE-MRI. Three kinetic models were applied to estimate Ktrans and fractional blood plasma volume (vp). We applied the Tofts and Kermode (TK) model without arterial input function (AIF) estimation, the TK model modified to include vp and AIF estimation (mTK), and a "first pass" variant of the TK model (FP). RESULTS: KTK values were considerably higher than KmTK and KFP values (P <0.001). KmTK and KFP were more comparable and closely correlated (rho=0.744), with KmTK generally higher than KFP (P <0.001). Estimates of vp(mTK) and vp(FP) also showed a significant difference (P <0.001); however, these values were very closely correlated (rho=0.901). KTK parameter maps showed "pseudopermeability" effects displaying numerous vessels. These were not visualized on KmTK and KFP maps but appeared on the corresponding vp maps, indicating a failure of the TK model in commonly occurring vascular regions. CONCLUSION: Both of the methods that incorporate a measured AIF and an estimate of vp provide similar pathophysiological information and avoid erroneous overestimation of Ktrans in areas of significant vessel density, and thus allow a more accurate estimation of endothelial permeability.

Adult↗
PubMed2003

E. coli selection of human genes encoding secreted and membrane proteins based on cDNA fusions to a leaderless beta-lactamase reporter.

Although several signal peptide-trapping methods have been devised and used to detect signal sequences, none have relied on using E.coli to identify eukaryotic proteins with signal peptides. Here, we describe a system for selecting human secreted and membrane proteins in E. coli followed by the direct validation of secretion in human cells. The method is based on cDNA fusions to a leaderless beta-lactamase reporter gene to isolate clones encoding signal peptides of human genes. We found that beta-lactamase fusion proteins carrying a eukaryotic signal peptide at its N-terminus were able to direct their export into the periplasm in E. coli to confer survival upon challenge with carbenicillin. When libraries constructed from 5' end-enriched cDNAs fused to beta-lactamase were screened in E.coli, approximately 0.5%-1% of the cDNAs are selected, and over half of the surviving clones were found to encode for secreted fusion proteins when tested in human cells. These clones were sequenced and shown to represent human genes encoding signal peptides of secreted and membrane proteins. We conclude that this is an efficient and effective strategy to easily enrich cDNA libraries for the identification of novel genes likely to encode secreted enzymes, growth factors, and receptors.

Base Sequence↗
PubMed2003

New hybrid technique for accurate and reproducible quantitation of dynamic contrast-enhanced MRI data.

The accuracy and precision of two major approaches for analyzing dynamic MRI data from the first passage of a Gd-DTPA contrast bolus are examined, using a Monte Carlo simulation. Method 1 fits the contrast concentration curve of the first pass to a two-compartment kinetic model to determine the tissue pharmacokinetic parameters. Method 2 decomposes intravascular and interstitial components of the first-pass curve based on a leakage profile (LP) model. Based on the results of these Monte Carlo simulations, a new "hybrid" method is proposed that combines both analytical approaches to optimize accuracy and precision of estimates of K(trans), v(e), and v(p). The new method was evaluated by computer simulation and used on experimental results from a patient with primary brain tumors. The new method has the potential to provide more accurate quantification of tissue plasma volume and vessel permeability.

Blood Volume↗
PubMed2003

Energy balance in predialysis patients on a low-protein diet.

OBJECTIVE: To determine if energy intake on a low-protein diet (0.6 g protein/kg ideal body weight (ibw)/d) with 70% animal protein (Diet A) or 30% animal protein (Diet B) meets energy expenditure derived from measured resting energy expenditure and activity levels. DESIGN: Patients already on a conventional low-protein diet with 70% animal protein kept a 5-day weighed dietary intake, with a 3-day activity diary, and had their resting metabolic rate (RMR) measured. Patients then switched to a diet with 30% animal protein for a minimum of 2 weeks (range, 2 to 16 weeks) and repeated the weighed intake and RMR measurement. SETTING: Predialysis hospital outpatients. PATIENTS: Seven patients were recruited, 5 male. Mean age, 56 years (range, 43 to 78 years); mean serum creatinine 300 micromol/L (range, 180 to 560 micromol/L). INTERVENTION: Indirect calorimetry used to measure RMR. MAIN OUTCOME MEASURE: RMR compared with standard formulae and total energy expenditure compared with dietary intake. RESULTS: Mean RMR was 5.76 MJ/d (1,385 kcal/d) or 84.9 kJ/kg ibw/d (20.3 kcal/kg ibw/d); which was 108% to 113% of that predicted by standard formulae. Total energy expenditure (RMR plus activity) was 8.35 MJ/d (1,996 kcal/d) or 123.3 kJ/kg/d (29.5 kcal/kg ibw/d). Mean energy intake was 116.3 (27.8 kcal/kg ibw/d) on Diet A and 131.2 (31.4 kcal/kg ibw/d) on Diet B (P = .096) with 3 of the 7 patients meeting their energy expenditure on Diet A and 4 on Diet B. CONCLUSION: RMR of patients with chronic renal failure is within expected range for healthy individuals, and the activity of these relatively fit patients similar to healthy individuals with light to moderate activity. Energy intake on the low-protein diets failed to meet energy expenditure in 4 patients on Diet A and 3 patients on Diet B. Low energy intake may contribute to the development of malnutrition in some patients.

Adult↗
PubMed2003

Virtual reality modelling language: freely available cross-platform visualization technique for 3-D visualization of the inner ear.

This was a study of the use of virtual reality modelling language (VRML) for cross-platform interactive three-dimensional (3-D) visualization of high-resolution magnetic resonance (MR) images of the inner ear in the assessment of cochlear implant candidates. A retrospective case review was made of cochlear implant candidates undergoing pre-operative high-resolution MR studies to determine their suitability for implantation. 3-D visualizations of MR scans of the inner ear structures were created using surface rendering and exported as portable VRML files. Case studies are presented to illustrate different points of interest. VRML reconstructions aided the interpretation of two-dimensional (2-D) source images in a variety of inner ear abnormalities. VRML is an internationally recognized standard for cross-platform 3-D visualization that creates a means of providing the implanting surgeon with a portable 3-D representation of the inner ear, aiding interpretation of the complex cross-sectional anatomy of these structures, and guiding selection of patients for implantation as well as implantation technique. The elucidation of the mechanisms behind inner ear malformations can also be aided by detailed imaging studies of the temporal bone, with VRML reconstructions providing an easily interpreted representation of deformities.

Adolescent↗
PubMed2003

Neoangiogenesis in association with moyamoya syndrome shown by estimation of relative recirculation based on dynamic contrast-enhanced MR images.

BACKGROUND AND PURPOSE: This study examined abnormalities of the recirculation phase of the contrast medium concentration time course curve in patients with moyamoya disease by using the relative recirculation (rR) parameter. Our aims were to increase understanding of the rR parameter and to assess its possible value in the investigation of moyamoya disease. METHODS: Six patients with confirmed moyamoya disease and five normal participants were examined by using dynamic T2*-weighted MR perfusion imaging. Parametric maps of relative cerebral blood volume, time to peak (TTP), and rR were calculated. The width of the normal distribution of TTP and the normal upper limit for rR were derived from the normal participants by identification of the 97.5% confidence limits for the distributions. Major vessels were identified by selection of pixels with relative cerebral blood volume >0.5. Areas of abnormally prolonged TTP and of increased rR were then identified in patients, and the relationship between these parameters and major vessels was examined. RESULTS: The combination of cerebral blood volume >50%, elevated TTP, and elevated rR values accurately identified areas of moyamoya vessel formation seen on angiograms. Larger well-developed meningeal and basal collaterals did not show abnormalities of rR. Areas of prolonged TTP were also observed to occur in the brain distal to arterial occlusion in all cases. In three of these, abnormal elevation of rR was observed in the center of regions of prolonged TTP. CONCLUSION: These findings support those of our previous work, which suggested that rR can act as an indicator of regional microvascular abnormality, such as that seen in areas of angiogenic activity. They also suggest that measurement of rR may provide valuable additional information regarding patients with moyamoya disease.

Adolescent↗
PubMed2002

Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: implications for trial design of antiangiogenic antibodies.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic cytokine, and various inhibitory agents, including specific antibodies, have been developed to block VEGF-stimulated angiogenesis. We developed HuMV833, a humanized version of a mouse monoclonal anti-VEGF antibody (MV833) that has antitumor activity against a number of human tumor xenografts, and investigated the distribution and biologic effects of HuMV833 in patients in a phase I trial. METHODS: Twenty patients with progressive solid tumors were treated with various doses of HuMV833 (0.3, 1, 3, or 10 mg/kg). Positron emission tomography with (124)I-HuMV833 was used to measure the antibody distribution in and clearance from tissues. Magnetic resonance imaging was used to measure the vascular permeability surface area product with a first-pass pharmacokinetic model (k(fp)) to determine tumor vascular permeability. RESULTS: The antibody was generally well tolerated, although the incremental dose, phase I study design, and pharmacodynamic endpoints could not identify the optimum biologically active dose. Antibody distribution and clearance were markedly heterogeneous between and within patients and between and within individual tumors. HuMV833 distribution to normal tissues also varied among patients, but the antibody was cleared from these tissues in a homogeneous fashion. Permeability was strongly heterogeneous between and within patients and between and within individual tumors. All tumors showed a reduction in k(fp) 48 hours after the first treatment (median = 44%; range = 4%-91%). CONCLUSIONS: Because of the heterogeneity in tumor biology with respect to antibody uptake and clearance, we suggest that either intrapatient dose escalation approaches or larger, more precisely defined patient cohorts would be preferable to conventional strategies in the design of phase I studies with antiangiogenic compounds like HuMV833.

Animals↗
PubMed2002

Dementing disorders: volumetric measurement of cerebrospinal fluid to distinguish normal from pathologic findings -- feasibility study.

The authors describe a magnetic resonance (MR) imaging technique to quantify the severity and distribution of cerebral atrophy by using automated volumetric analysis of the distribution of cerebrospinal fluid. The MR imaging technique demonstrated high diagnostic sensitivity and specificity in a group of healthy subjects and patients with dementing diseases. The authors conclude that this approach provides valuable clinical information that is complementary to information acquired with standard diagnostic practices.

Age Factors↗
PubMed2002

Abnormalities in the recirculation phase of contrast agent bolus passage in cerebral gliomas: comparison with relative blood volume and tumor grade.

BACKGROUND AND PURPOSE: Abnormalities in the recirculation phase of the passage of a contrast agent bolus have been identified in tumors and have been suggested to represent vascular tortuosity and hypoperfusion in areas of angiogenic neovascularization. This study was performed to examine the hypothesis that these abnormalities provide information concerning the microcirculation related to tumor grade in patients with cerebral glioma. METHODS: Contrast-enhanced dynamic susceptibility MR imaging was performed in 27 patients with glioma. Residual relaxivity effects were minimized by injection of contrast agent before dynamic imaging. Maps of relative cerebral blood volume (rCBV) and relative recirculation (rR) were calculated, and values from enhancing tumor tissue were compared with tumor grade. RESULTS: Histologic grades were grade II, astrocytoma (n = 3); grade III, anaplastic astrocytoma (n = 10); and grade IV, glioblastoma multiforme (n = 14). rCBV values varied among tumor grades, with higher mean values in higher grade tumors (P <.001). Mean rR values in grade II tumors were not significantly different from those in normal gray and white matter. Mean rR values in grades III and IV tumors were similar and were significantly higher than those in grade II tumors (P <.01). The distribution of the pixel values of rR showed significant differences between grades III and IV tumors (P <.001), with low values of skewness in keeping with a normal distribution in grade III tumors and higher values in grade IV tumors. CONCLUSION: Variation in the recirculation characteristics of a contrast agent bolus is related to tumor grade in gliomas. This supports the hypothesis that abnormalities in contrast agent recirculation provide independent information concerning the microcirculation in imaging studies of angiogenesis and may be of value as surrogate markers in trials of antiangiogenic therapy.

Adult↗
PubMed2002

Using Bayesian tissue classification to improve the accuracy of vestibular schwannoma volume and growth measurement.

BACKGROUND AND PURPOSE: True 3D measurements of tumor volume are time-consuming and subject to errors that are particularly pronounced in cases of small tumors. These problems complicate the routine clinical assessment of tumor growth rates. We examined the accuracy of currently available methods of size and growth measurement of vestibular schwannomas compared with that of a novel fast partial volume tissue classification algorithm. METHODS: Sixty-three patients with unilateral sporadic vestibular schwannomas underwent imaging. Thirty-eight of these patients underwent imaging two or more times at approximately 12-month intervals. Contrast-enhanced 3D T1-weighted images were used for all measurements. An experienced radiologist performed standard size estimations, including maximal diameter, elliptical area, perimeter, manually segmented area, intensity thresholded seeding volume, and manually segmented volume. A method for calculating volume was also used, incorporating Bayesian probability statistics to estimate partial volume effects. Manually segmented volume was obtained as a baseline standard measure. A computer-generated phantom exhibiting the intensity and partial volume characteristics of brain tissue, CSF, and intracanalicular vestibular schwannoma tissue was used to measure absolute accuracy of the standard technique and Bayesian partial volume segmentation. RESULTS: The Bayesian partial volume segmentation method showed the highest correlation (R(2) = 0.994) with the standard method, whereas the commonly used method of maximal diameter measurement showed poor correlation (R(2) = 0.732). Accuracy of Bayesian segmentation was shown to be more than twice that of manual segmentation, with an absolute accuracy of 5% (cf, 13%) and a remeasurement accuracy of 70 mm(3) (cf, 150 mm(3)). For the 38 patients who underwent imaging twice, definite tumor growth was shown for 12, potential growth for seven, no growth for 17, and definite shrinkage for two. CONCLUSION: Commonly used methods such as maximal diameter measurements do not provide adequate statistical accuracy with which to monitor tumor growth in patients with small vestibular schwannomas. Bayesian partial volume segmentation provides a more accurate and rapid method of volume and growth estimation. These differences in measurement accuracy translated into a significant improvement in clinical assessment, allowing identification of tumor growth in 10 of 12 cases that appeared to be static in size when manual segmentation techniques are used. The technique is quick to perform and suitable for use in routine clinical practice.

Adult↗