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Biomedical subjects

A Jackson

Publications and source records attributed to A Jackson.

At least 73 records · Page 4Linked to original sources
PubMed2001

Late rectal bleeding after conformal radiotherapy of prostate cancer. II. Volume effects and dose-volume histograms.

PURPOSE AND OBJECTIVE: Late rectal bleeding is a potentially dose limiting complication of three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. The frequency of late rectal bleeding has been shown to increase as the prescription dose rises above 70 Gy. The purpose of this study is to identify features of the cumulative dose-volume histogram (DVH) for the rectal wall that correlate with late rectal bleeding after 3D-CRT for prostate cancer. METHODS AND MATERIALS: Follow-up information on rectal bleeding is available for 261 and 315 patients treated using 3D-CRT at Memorial Sloan-Kettering Cancer Center for Stage T1c-T3 prostate cancer with minimum target doses of 70.2 and 75.6 Gy, respectively. All patients in this study were treated with a coplanar 6-field technique (2 lateral and 4 oblique fields). Patients were classified as having rectal bleeding if they bled (> or = Grade 2) before 30 months, and nonbleeding (< or = Grade 1) if they were without bleeding at 30 months, using the RTOG morbidity scale. Rectal bleeding was observed in 13 and 38 of the patients treated at 70.2 and 75.6 Gy, respectively. Treatment plans were analyzed for 39 nonbleeding and 13 bleeding patients receiving 70.2 Gy, and 83 nonbleeding and 36 bleeding patients receiving 75.6 Gy. Dose-volume histograms (DVHs) for the anatomic rectal wall were calculated. Average DVHs of the bleeding and nonbleeding patients were generated, and a permutation test was used to assess the significance of differences between them, for each dose group. The confounding effect of total rectal wall volume (V(RW)) was removed by calculating the average differences in DVHs between all combinations of bleeding and nonbleeding patients with similar V(RW)s. Finally, multivariate analysis using logistic regression was performed to test the significance of the DVH variables in the presence of anatomic, geometric, and medical variables previously found to correlate with rectal bleeding in a companion analysis of the same patients. RESULTS: The area under the average percent volume DVH for the rectal wall of patients with bleeding was significantly higher than those of patients without bleeding in both dose groups (p = 0.02, 70.2 Gy; p < 0.0001, 75.6 Gy). However, small V(RW)s were associated with rectal bleeding (p = 0.06, 70.2 Gy; p < 0.01, 75.6 Gy), resulting in an increase in average percent volumes exposed to all doses for patients with rectal bleeding. For patients with similar V(RW)s, rectal bleeding was significantly correlated with the volumes exposed to 46 Gy in both dose groups (p = 0.02, 70.2 Gy; p = 0.005, 75.6 Gy, tolerance in V(RW): 5 ccs). For the 75.6 Gy dose group, the percent volume receiving 77 Gy was significantly correlated with rectal bleeding (p < 0.005). Bivariate analysis using logistic regression, including V(RW) together with a single DVH variable, showed good agreement with the above analysis. Multivariate analysis revealed a borderline significant correlation of the percent volume receiving 71 Gy in the 70.2 Gy dose group. It also showed that the DVH variables were highly correlated with geometric and dosimetric variables previously found to correlate with rectal bleeding in multivariate analysis. CONCLUSION: Significant volume effects were found in the probability of late rectal bleeding for patients undergoing 3D-CRT for prostate cancer with prescription doses of 70.2 and 75.6 Gy. The percent volumes exposed to 71 and 77 Gy in the 70.2 and 75.6 Gy dose groups respectively were significantly correlated with rectal bleeding. The independent correlation of small V(RW) with rectal bleeding may indicate the existence of a functional reserve for the rectum. The independent association with larger percent volumes exposed to intermediate doses ( approximately 46 Gy) seen in both dose groups may indicate that a large surrounding region of intermediate dose may interfere with the ability to repair the effects of a central high dose region.

Algorithms↗
PubMed2001

The problem of uniqueness of fit for viscoelastic films on thickness-shear mode resonator surfaces.

We describe a new strategy for interpreting frequency responses of thickness shear mode resonators loaded with spatially uniform viscoelastic films. This procedure leads to unambiguous extraction of the four parameters that characterize such a film: its thickness, density and shear modulus components (storage and loss moduli). The interpretational difficulty is that the experimental frequency response (impedance spectrum) can only provide two parameters; thus, the problem is underdetermined. Previous interpretations employed various approximations and assumptions for two (or more) film parameters to effectively reduce the problem to a two-parameter fit. Such approaches are clearly imperfect. Our new strategy splits the problem into two separate two-parameter sub-problems, each of which is solved by the measurement of two different experimental responses. The result is a unique fit to the data without the need to make approximations or assumptions for film parameters. First, in the acoustically thin regime, measured frequency shift and film charge are combined to provide a unique solution for film thickness and density; shear moduli components do not affect the response in this regime. Second, film density is carried forward directly, and the film thickness-charge relationship is extrapolated into the acoustically thick regime. Third, with film density and thickness held fixed, crystal impedance data in the acoustically thick regime provide unambiguous shear modulus components. The method is generalized to any other (nonelectrochemical) probe that provides film thickness data and validated using crystal impedance data for poly(3-methylthiophene) films exposed to propylene carbonate.

Journal Article↗
PubMed2001

Regional cerebral volume measurements in late-life depression: relationship to clinical correlates, neuropsychological impairment and response to treatment.

BACKGROUND: Elderly people who develop depression have demonstrable changes in cerebral structure but little is known of the relationship between regional cerebral volumes, treatment response and cognitive impairment. METHOD: Forty-four patients with major depression diagnosed according to DSM-IIIR criteria underwent magnetic resonance imaging and regional cerebral volumes were quantified using multispectral analysis. Response to antidepressant treatment was assessed prospectively and a neuropsychological test battery was administered. RESULTS: There was a trend for smaller fronto-temporal volumes in the treatment-resistant patients. Impaired immediate working memory was linked with reduced frontal and parietal lobe volume and impaired short-term memory functioning was associated with reduced temporal lobe volume. Ventricular enlargement was associated with prior administration of electro-convulsive therapy, poor physical health and later age at onset of first episode of depression. CONCLUSION: In late-life depression, brain changes should not preclude vigorous antidepressant treatment. Regional cerebral volume changes may be a complication of poor physical health and are associated with memory dysfunction even upon recovery from depression.

Age Factors↗
PubMed2001

Reproducibility of T2* blood volume and vascular tortuosity maps in cerebral gliomas.

The development of anti-angiogenic therapies for tumors has led to a demand for imaging-based surrogate markers of the angiogenic process. The utility of such markers is highly dependent on their test-retest reproducibility. This paper presents a formal assessment of the reproducibility of measurements of relative blood volume (rBV), normalized rBV (rBVnorm), and vascular tortuosity as estimated by measurement of relative recirculation (rR). The study was conducted in 11 patients with glioma who were scanned on two occasions 36-56 hours apart. The observed reliability estimates were used to calculate 95% confidence limits for detection of differences between groups and for changes in individual cases. The results show that measurement of rBV or rBVnorm in consecutive studies is statistically capable of reliably detecting changes in excess of 15% in between group studies and 25% in individual patients. Measurement of vascular tortuosity using is less reproducible but is able to confidently identify changes in excess of 30% in group studies and 35% in individuals.

Blood Volume↗
PubMed2001

Improved high resolution MR imaging for surface coils using automated intensity non-uniformity correction: feasibility study in the orbit.

This study examined the effects of a recently developed automated intensity non-uniformity correction on surface coil images using the orbit as an exemplar. Images were obtained using a standard head coil and a range of surface coils. Slices through the optic nerve head and cavernous sinus were subjected to the correction algorithm. Blind forced-choice rankings of the subjective image quality were performed. Quantitative measurements were taken of the similarity between vitreous humor at two depths from the coil, and of the conspicuity between orbital fat and temporalis muscle intensities. The combined qualitative ranks for corrected surface coil images were higher than for the equivalent uncorrected images in all cases. Intensity non-uniformity correction produced statistically significant improvements in orbital surface coil images, bringing their intensity uniformity in homogeneous tissue to the level of head coil images. The subjective quality of the corrected surface coil images was superior to head coil images, due to increased spatial resolution combined with improved signal to noise ratio across the image.

Algorithms↗
PubMed2001

A low dose alcohol drug discrimination in social drinkers: relationship with subjective effects.

RATIONALE: Although well characterised in animals, relatively little is known about alcohol discriminative stimulus effects in humans. OBJECTIVE: The study was carried out to investigate the correspondence of subjective effects and the discriminative response during the acquisition of a low dose alcohol discrimination in humans. METHODS: Healthy volunteers completed an Alcohol Use Questionnaire and were then trained to discriminate a dose of 0.2 g/kg alcohol from placebo using a money reinforced technique. Subjects sampled drinks during training, but also completed rating scales measuring Taste, Like/Dislike and Subjective Effects for each drink. RESULTS: Thirty-two subjects learned the discrimination (discriminators; Ds). In these subjects, differences between placebo scores and alcohol scores for Lightheadedness, Relaxed, Arousal and Fatigue were greater following acquisition of the discrimination, compared with differences at the start of training. Differences in other measures remained consistent. Twenty-six of the volunteers failed to learn the discrimination (non-discriminators; NDs). These subjects reported drinking approximately twice as much alcohol during the preceding 6 months, as the Ds (4.35+/-0.53 g/kg per week versus 2.08+/-0.19 g/kg per week, respectively, P<0.001). There were no alcohol specific differences in ratings for Lightheadedness, Relaxed, Arousal or Fatigue between the Ds and the NDs. However, Dislike scores did differentiate between the Ds and the NDs in that the NDs had reduced ratings for the alcohol drink only compared with the Ds (P<0.02). CONCLUSIONS: These results support the suggestion from animal studies, that the alcohol stimulus is a compound, and characterise the subjective effects which contribute to a low dose cue in humans. In addition, the data suggest that previous drinking experience may selectively alter aversive responses to alcohol and that this, in addition to differences in general arousal levels, may have affected subjects' ability to learn the discrimination.

Adolescent↗
PubMed2001

Estrogen modulates 5-HT(1A) agonist inhibition of lordosis behavior but not binding of [(3)H]-8-OH-DPAT.

Previous studies showed that repeated estrogen treatment reduces the ability of the 5-HT(1A) receptor agonist, 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT), to inhibit lordosis behavior of female rats. The present study evaluated the effects of repeated estrogen treatment on lordosis behavior and 5-HT(1A) receptor binding and coupling to G protein in the hypothalamus-preoptic area using the agonist ligand [3H]-8-OH-DPAT, which binds selectively to G-protein-coupled 5-HT(1A) receptors. Rats were injected twice with 25 or 50 microg of estradiol benzoate (EB) 7 days apart followed by 500 microg of progesterone (P) 48 h after the second EB injection. Controls received a single injection of 25 or 50 microg EB followed 48 h later by 500 microg of P. Four hours after P, 0.15 mg/kg 8-OH-DPAT was injected, and lordosis behavior examined for 30 min. Rats treated twice with EB showed significantly less 8-OH-DPAT inhibition of lordosis behavior than rats receiving a single EB injection. For receptor binding, rats received EB without P treatment. None of the estrogen treatments reduced [3H]-8-OH-DPAT binding density or affinity in the hypothalamus-preoptic area or hippocampus. These studies suggest that estrogen modulates 5-HT(1A) agonist potency without a measurable change in 5-HT(1A) receptor density or coupling to G protein.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

The cytoplasmic tail of the D1A receptor subtype: identification of specific domains controlling dopamine cellular responsiveness.

In this study the rat D1A receptor (wild-type, WT) and truncation mutants thereof, are utilized to delineate specific cytoplasmic tail (CT) domains responsible for regulating ligand binding and receptor-mediated adenylyl cyclase activation. In human embryonic kidney (HEK) cells, all truncation mutants of the D1A receptor (Delta425, Delta379, Delta351) display cell surface localization and express at high but different receptor numbers. Binding studies suggest that residues located between Cys(351) and Asp(425) may serve to restrain the agonist binding conformation of the D1A receptor. This contention is supported by the observation that the constitutive activation of Delta351 is significantly increased in comparison with WT, Delta425 and Delta379. Furthermore, we demonstrate that the extent of dopamine-mediated maximal activation of adenylyl cyclase is significantly augmented in cells expressing Delta351 when compared with WT or mutants harboring shorter truncations. These results suggest that in addition to restraining receptor conformation, determinants located downstream of Cys(351) may act as negative regulators of the G protein coupling efficiency and adenylyl cyclase activation. Interestingly, all truncated receptors used in the present study display a decrease in dopamine potency when compared with WT. We show that inhibition of protein kinase A (PKA) activity leads also to a reduction in dopamine potency in cells expressing WT but not Delta351 receptors. These results hint at a potential previously unanticipated role for PKA in facilitating D1A receptor coupling efficiency in HEK cells. Overall, the present study has uncovered specific CT domains involved in regulating discrete aspects of the D1A receptor signaling.

Adenylyl Cyclases↗
PubMed2001

Partial irradiation of the rectum.

Data gathered from dose escalation protocols for the treatment of prostate cancers conducted in the past 10 years have shown that rectal toxicity can be controlled by the use of careful conformal techniques. The most severe complications of rectal irradiation (obstruction and fistula requiring colostomy) have been essentially eliminated. The most frequent gastrointestinal complications of conformal radiotherapy of prostate cancer are now rectal bleeding associated with telangiectatic changes to the vasculature of the submucosa, and in severe cases, ulceration requiring cautery procedures and or transfusion. The benefits of 3-dimensional conformal radiotherapy (3D-CRT) are strongly technique dependent, with a strong dose response for single techniques for prescription doses over 70 Gy. Studies of rectal motion show that the anterior wall can move approximately 1 cm during treatment, so portions of the anterior rectal wall will regularly receive the full prescription dose if posterior margin sizes >/= 1 cm are used in designing the planning target volume (PTV). There is strong evidence that increased rectal shielding and posterior PTV margin sizes approximately 0.6 cm reduce rectal complication rates. Despite uncertainties due to rectal motion, studies of dose-volume histograms (DVHs) show that rectal toxicity is strongly influenced by the percent volumes of rectal wall exposed to doses approximately 70 Gy and higher. Recent data suggests that percent volumes of rectal wall exposed doses between 40 to 50 Gy, and the existence of a reserve of unexposed tissue may also play a role in determining rectal bleeding rates.

Dose-Response Relationship, Radiation↗
PubMed2001

Significance of CSF area measurements in cervical spondylitic myelopathy.

Mild clinical myelopathy can occur without cord compression, and asymptomatic cord compression seen on MRI is common. The aim of this study was to ascertain the MRI features which best correlate with early clinical myelopathy. The study was conducted on three groups: group A, 20 patients with clinical myelopathy and MRI evidence of cervical spondylosis; group B, 20 patients without myelopathy, but with other clinical and MRI evidence of cervical spondylosis; and group C, 10 normal volunteers with no MRI evidence of spondylosis. The cross-sectional area (CSA) of the spinal cord (SP-CSA), spinal canal (SC-CSA) and CSF space (CSF-CSA) were measured on T1-weighted axial images at the level of the most severe spinal canal stenosis. The severity of myelopathy was assessed using a simple scoring system giving a score from 0 (normal) to 11 (severe). Subjective demonstration of cord compression on sagittal images was an insensitive indicator of clinical myelopathy. All three measures of cross-sectional area were significantly smaller in Group A than in B (p<0.01). The reduction in SP-CSA was the only independent prognosticator for severity of myelopathy (p<0.005) accounting for 63% of the variation in myelopathy score. All three variables showed a significant correlation with the presence of myelopathy (p<0.01); however, logistic regression analysis showed a decrease in CSF-CSA to be the only independent significant prognosticator of the presence of clinical myelopathy (p<0.02). Reduction of the CSF space to less than 0.7 cm2 was associated with a 90% chance of clinical myelopathy (specificity 83%).

Adult↗
PubMed2001

CAMPATH-1M T-cell depleted BMT for SCID: long-term follow-up of 19 children treated 1987-98 in a single center.

BACKGROUND: SCID can be cured by BMT. Depletion of mature T cells from BM has enabled HLA non-identical stem-cell transplantation. We report the outcome of 30 patients treated with 37 T-cell depleted BMT procedures using CAMPATH-1M in vitro between 1987-98 in a single center. METHODS: Immune reconstitution and quality-of-life were assessed in 19 longterm survivors. All but two received pre-transplant conditioning. T- and B-cell chimerism, numbers and function were analyzed during a median follow-up of 5.3 years (range 1.33-12). RESULTS: The overall engraftment rate was 59%, six children required repeated BMT and the survival rate was 63%. All have donor T cells, 58% normal T-cell numbers and 74% normal T-cell function. Of 17 evaluated, 16 patients (94%) have normal IgM and IgG levels, and production of specific Abs to protein Ags, but only 5/16 (31%) have a good response to pneumococcal polysaccharide. Early and late post-BMT complications were rare and there were no delayed deaths. Only one child continues on long-term i.v. Ig 4-years post-BMT. Eleven children died (37%). DISCUSSION: CAMPATH-1M T-cell depleted BMT for SCID resulted in 63% survival. Deaths of 11 children were mainly due to pre-existing infections. Seventeen of 19 long-term survivors have normal immune function and good quality-of-life.

Alemtuzumab↗
PubMed2001

Bayesian estimation of fold-changes in the analysis of gene expression: the PFOLD algorithm.

A general and detailed noise model for the DNA microarray measurement of gene expression is presented and used to derive a Bayesian estimation scheme for expression ratios, implemented in a program called PFOLD, which provides not only an estimate of the fold-change in gene expression, but also confidence limits for the change and a P-value quantifying the significance of the change. Although the focus is on oligonucleotide microarray technologies, the scheme can also be applied to cDNA based technologies if parameters for the noise model are provided. The model unifies estimation for all signals in that it provides a seamless transition from very low to very high signal-to-noise ratios, an essential feature for current microarray technologies for which the median signal-to-noise ratios are always moderate. The dual use, as decision statistics in a two-dimensional space, of the P-value and the fold-change is shown to be effective in the ubiquitous problem of detecting changing genes against a background of unchanging genes, leading to markedly higher sensitivities, at equal selectivity, than detection and selection based on the fold-change alone, a current practice until now.

Algorithms↗
PubMed2001

A study of the cortical processing of ano-rectal sensation using functional MRI.

Investigation of human ano-rectal physiology has concentrated largely on understanding the motor control of defecation and continence mechanisms. However, little is known of the physiology of ano-rectal sensation. There are important differences in the afferent innervation and sensory perception between the rectum and anal canal. This suggests that there could also be differences in the brain's processing of sensation from these two areas; however, this possibility remains unexplored. The aim of our study was to identify the cerebral areas processing anal (somatic) and rectal (visceral) sensation in healthy adults, using functional MRI. Eight male subjects with an age range of 21-39 years were studied on two separate occasions, one for rectal and the other for anal stimulation studies. Single shot gradient echo planar imaging was performed using a 1.5 tesla Phillips MRI scanner. For each subject, a series of 40 image sets containing 24 slices of the brain was obtained during periods of rapid phasic non-painful distension of the rectum or anal canal, alternating with rest periods, without stimulation. After motion correction, the images were analysed using cross correlation to identify the cerebral areas activated by the stimulus. Rectal stimulation resulted in bilateral activation of the inferior primary somatosensory, secondary somatosensory, sensory association, insular, peri-orbital, anterior cingulate and prefrontal cortices. Anal canal stimulation resulted in activation of areas similar to rectal stimulation, but the primary somatosensory cortex was activated at a more superior level, and there was no anterior cingulate activation. In conclusion, anal and rectal sensation resulted in a similar pattern of cortical activation, including areas involved with spatial discrimination, attention and affect. The differences in sensory perception from these two regions can be explained by their different representation in the primary somatosensory cortex. The anterior cingulate cortex was only activated by rectal stimulation, suggesting that the viscera have a greater representation on the limbic cortex than somatic structures, and this explains the greater autonomic responses evoked by visceral sensation in comparison with somatic sensation.

Adult↗
PubMed2001

Risk factor distribution among sociodemographically diverse African American adults.

Because African Americans tend to have lower socioeconomic status (SES) than whites and numerous health indicators are related to SES variables, it is important when examining between-group differences in health indices to account for SES differences. This study examined the effects of income and education on several biologic and behavioral risk factors in a sample of sociodemographically diverse African American adults. Approximately 1,000 African American adults (aged 18-87) were recruited from 14 churches with predominantly black membership to participate in a nutrition education intervention. Demographics, height, weight, blood pressure, self-reported cigarette and alcohol use, self-reported diet by food frequency questionnaire, serum carotenoids, serum total cholesterol, and nutrition knowledge were assessed. The association of these risk factors were examined by four levels of education and income. For men, body mass index, blood pressure, total cholesterol, daily intake of fruits and vegetables, serum carotenoids, heavy alcohol use, or exercise were not associated significantly with income or education using analysis of variance (ANOVA). Past month alcohol use and nutrition knowledge were associated positively with education, but not income. For women, body mass index and smoking were associated inversely with income, but not with education. Blood pressure, total cholesterol, intake of fruits and vegetables, heavy alcohol use, and exercise were not associated with either income or education using ANOVA. Serum carotenoids, any 30-day alcohol use, and nutrition knowledge were associated positively with both income and education. Results using linear regression generally were similar for men and women, although a few more variables were associated significantly with SES compared to ANOVA analyses. Several health indicators that have been associated with socioeconomic variables in whites were not associated or only weakly associated in this diverse sample of African Americans. One interpretation of these findings is that SES factors may function differently among blacks and whites.

Adolescent↗
PubMed2001

Synchronization in monkey motor cortex during a precision grip task. I. Task-dependent modulation in single-unit synchrony.

Neural synchronization in the cortex, and its potential role in information coding, has attracted much recent attention. In this study, we have recorded long spike trains (mean, 33,000 spikes) simultaneously from multiple single neurons in the primary motor cortex (M1) of two conscious macaque monkeys performing a precision grip task. The task required the monkey to use its index finger and thumb to move two spring-loaded levers into a target, hold them there for 1 s, and release for a food reward. Synchrony was analyzed using a time-resolved cross-correlation method, normalized using an estimate of the instantaneous firing rate of the cell. This was shown to be more reliable than methods using trial-averaged firing rate. A total of 375 neurons was recorded from the M1 hand area; 235 were identified as pyramidal tract neurons. Synchrony was weak [mean k' = 1.05 +/- 0.04 (SD)] but widespread among pairs of M1 neurons (218/1359 pairs with above-chance synchrony), including output neurons. Synchrony usually took the form of a broad central peak [average width, 18.7 +/- 8.7 (SD) ms]. There were marked changes during different phases of the task. As a population, synchrony was greatest during the steady hold period in striking contrast to the averaged cell firing rate, which was maximal when the animal was moving the levers into target. However, the modulation of synchrony during task performance showed considerable variation across individual cell pairs. Two types of synchrony were identified: oscillatory (with periodic side lobes in the cross-correlation) and nonoscillatory. Their relative contributions were quantified by filtering the cross-correlations to exclude either frequencies from 18 to 37 Hz or all higher and lower frequencies. At the peak of population synchrony during the hold period, about half (51.7% in one monkey, 56.2% in the other) of the synchronization was within this oscillatory bandwidth. This study provides strong support for assemblies of neurons being synchronized during specific phases of a complex task with potentially important consequences for both information processing within M1 and for the impact of M1 commands on target motoneurons.

Action Potentials↗
PubMed2001

Mathematical segmentation of grey matter, white matter and cerebral spinal fluid from MR image pairs.

The aims of this study were (1) to design a mathematical segmentation technique to allow extraction of grey matter, white matter and cerebral spinal fluid volumes from paired high resolution MR images and (2) to document the statistical accuracy of the method with different image combinations. A series of linear equations were derived that describe proportional tissue volumes in individual image voxels. The equations use estimates of pure tissue values to derive the proportion of each tissue within a single voxel. Repeatability of manual estimations of pure tissue values was assessed both using regions of interest and thresholding techniques. Statistical accuracy of tissue estimations for a variety of image pairs was assessed from measurements of root-mean-square noise and mean grey level intensity. The technique was used to produce parametric images of grey and white matter distribution. The segmentation technique showed greatest statistical accuracy when the first image has high grey/white matter contrast and the second image has little contrast or the rank order of the signal intensities from pure tissue is reversed. A combination of inversion recovery fast spin echo and fast FLAIR images produced a statistical error of 11% for grey matter and 10% for white matter for any given voxel. The effect of increasing sample size improves both of these figures to give a 1% statistical error on a 100 pixel sample.

Algorithms↗