Search PubMed⌕ Search

Biomedical subjects

R Myers

Publications and source records attributed to R Myers.

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

Validation of advanced ECG diagnostic software for the detection of prior myocardial infarction by using nuclear cardiac imaging.

The investigators report the diagnostic performance of the latest version (Version 2.5) of the recently developed Cardiovise algorithm for detecting prior myocardial infarction (MI). The Cardiovise 2.5 prior MI algorithm, a component of Cardiovise Cardiac Diagnostic System (Inovise Medical, Inc, Newberg, OR), uses scalar QRS, scalar T wave, and vectorcardiographic QRS criteria for detecting, sizing, and localizing prior MI. In this study only the detection part of the algorithm's performance was evaluated, using 105 patients with and 98 patients without prior MI as indicated by the results of cardiac imaging with Sestamibi. The specificity, and sensitivity of Cardiovise 2.5 for detecting prior MI in this population of patients are 97% and 79%, respectively. The sensitivity and overall diagnostic performance of Cardiovise 2.5 was significantly better than those of a total of 6 human readers (3 cardiologists and 3 primary care physicians) and to 2 commercially available ECG diagnostic algorithms.

Algorithms↗
PubMed2001

In vivo visualization of activated glia by [11C] (R)-PK11195-PET following herpes encephalitis reveals projected neuronal damage beyond the primary focal lesion.

A major challenge in the assessment of brain injury and its relationship to the ensuing functional deficits is the accurate delineation of the areas of damage. Here, we test the hypothesis that the anatomical distribution pattern of activated microglia, a normally dormant population of resident brain macrophages, can be used as a surrogate marker of neuronal injury not only at the primary lesion site but also in the antero- and retrograde projection areas of the lesioned neurones. Two patients with asymmetrical herpes simplex encephalitis were serially scanned 6 and 12 months after the acute illness using PET with [11C] (R)-PK11195, a marker of activated microglia/brain macrophages. The evolving structural changes in the brain were measured by volumetric MRI and compared with the pattern of [11C](R)-PK11195 binding. Corresponding to the clinically observed cognitive deficits, quantitative [11C](R)-PK11195-PET revealed highly significant signal increases within the affected limbic system and additionally in areas connected to the limbic system by neural pathways, including the lingual gyrus in the occipital lobe and the inferior parietal lobe, which had normal morphology on structural MRI. The increased [11C](R)-PK11195 binding, signifying the presence of activated microglia, persisted many months (>12) after antiviral treatment. Cortical areas that showed early high [11C](R)-PK11195 binding subsequently underwent atrophy. These observations demonstrate that in vivo imaging of activated microglia/brain macrophages provides a dynamic measure of active tissue changes following an acute focal lesion. Importantly, the glial tissue response in the wake of neuronal damage is protracted and widespread within the confines of the affected distributed neural system and can be related to the long-term functional deficits.

Adult↗
PubMed2001

The effect of isolated soy protein on plasma biomarkers in elderly men with elevated serum prostate specific antigen.

PURPOSE: We performed a randomized double-blind crossover pilot study in elderly men with elevated prostate specific antigen (PSA) on the effects of the daily consumption of 2 soy beverages, each containing 20 gm. of isolated soy protein, on the isoflavone concentration in blood and urine, and on the 3 serum biomarkers cholesterol, PSA and the soluble p105 component of the p185erbB-2 proto-oncogene. MATERIALS AND METHODS: A total of 34 men supplemented their diet by consuming 1 of 2 soy protein beverages assigned randomly twice daily for a 6-week period. In a second 6-week period they consumed the other soy protein beverage. The beverage ISP+ provided 42 mg. of genistein and 27 mg. of daidzein daily, whereas the other beverage, ISP-, provided only 2.1 and 1.3 mg. of these isoflavones daily, respectively. Blood and 24-hour urine samples were obtained before the study, at 2-week intervals during the study and 2 weeks after study completion. RESULTS: ISP+ and to a lesser extent ISP- substantially increased the serum concentration and urinary output of the isoflavones and their metabolites. Serum cholesterol was significantly decreased by ISP+ irrespective of the order in which the 2 soy beverages were administered and in apparent correlation with the total isoflavone concentration. There was no significant effect of the soy beverages on serum PSA and p105erbB-2 values. CONCLUSIONS: This study reveals that short-term exposure of elderly men with elevated serum PSA values to soy protein containing isoflavones decreases serum cholesterol but not the serum biomarkers PSA and p105erbB-2.

Aged↗
PubMed2001

Empirical modelling of genetic algorithms.

This paper addresses the problem of reliably setting genetic algorithm parameters for consistent labelling problems. Genetic algorithm parameters are notoriously difficult to determine. This paper proposes a robust empirical framework, based on the analysis of factorial experiments. The use of a graeco-latin square permits an initial study of a wide range of parameter settings. This is followed by fully crossed factorial experiments with narrower ranges, which allow detailed analysis by logistic regression. The empirical models derived can be used to determine optimal algorithm parameters and to shed light on interactions between the parameters and their relative importance. Refined models are produced, which are shown to be robust under extrapolation to up to triple the problem size.

Algorithms↗
PubMed2001

Role of AMP-activated protein kinase in mechanism of metformin action.

Metformin is a widely used drug for treatment of type 2 diabetes with no defined cellular mechanism of action. Its glucose-lowering effect results from decreased hepatic glucose production and increased glucose utilization. Metformin's beneficial effects on circulating lipids have been linked to reduced fatty liver. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. Here we report that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed. Activation of AMPK by metformin or an adenosine analogue suppresses expression of SREBP-1, a key lipogenic transcription factor. In metformin-treated rats, hepatic expression of SREBP-1 (and other lipogenic) mRNAs and protein is reduced; activity of the AMPK target, ACC, is also reduced. Using a novel AMPK inhibitor, we find that AMPK activation is required for metformin's inhibitory effect on glucose production by hepatocytes. In isolated rat skeletal muscles, metformin stimulates glucose uptake coincident with AMPK activation. Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders.

AMP-Activated Protein Kinases↗
PubMed2000

Thalamic microglial activation in ischemic stroke detected in vivo by PET and [11C]PK1195.

Using quantitative PET, the authors studied the binding of [11C]PK11195, a marker of activated microglia, in the thalamus of patients with chronic middle cerebral artery infarcts. All patients showed increased [11C]PK11195 binding in the ipsilateral thalamus, indicating the activation of microglia in degenerating projection areas remote from the primary lesion. A persistent increase in [11C]PK11195 binding suggests active, long-term thalamic microstructural changes after corticothalamic connection damage.

Adult↗
PubMed2000

Visual attention impairments in Alzheimer's disease.

BACKGROUND: Impaired attention can hinder information processing at multiple levels and may explain aspects of functional decline in aging and dementia. Impairments of attention in early AD may contribute to performance reductions in other cognitive domains, including memory and executive functions. METHOD: - The authors analyzed the scores on a battery of tests of attention and cognitive abilities in 64 older individuals: 42 with mild AD and 22 control subjects without dementia. The authors tested the hypotheses that patients with AD would have impairments of visual attention, and that these impairments would correlate with dysfunction in other key cognitive domains. RESULTS: Patients with AD performed significantly worse than control subjects on measures of sustained attention, divided attention, selective attention, and visual processing speed. The differences were not due to differences in age, education, or basic visual function. Strong relationships were identified between reduced attention skills and overall cognitive impairment. CONCLUSIONS: Deterioration of attention abilities occurs in early stages of AD, and likely contributes to functional decline in these patients. More routine assessment of visual attention deficits could give a more accurate measure of functionally useful perception in patients with AD who show normal visual acuity and visual fields, perhaps providing useful clues to diagnosis and staging.

Aged↗
PubMed2000

Rate-dependent changes of twitch force duration in rat cardiac trabeculae: a property of the contractile system.

1. We examined the mechanisms for rate-dependent changes in twitch force duration by simultaneously measuring force and [Ca2+]i in rat cardiac trabeculae. 2. Peak force decreased when the rate of stimulation was increased from 0.2 to 0.5 Hz, whilst it increased from 1 to 2 Hz. Over the same range of frequencies, peak [Ca2+]i transients increased monotonically, whilst both force and [Ca2+]i transient duration were abbreviated. 3. Changes in peak force or peak [Ca2+]i transients were not responsible for the changes in force or [Ca2+]i transient duration. 4. The changes in twitch force and [Ca2+]i transient duration were completed roughly within one beat following an abrupt change in the rate of stimulation. 5. Rate-dependent changes resembled those observed with isoproterenol (isoprenaline) application. However, kinase inhibitors (i.e. K252-a, H-89, KN-62 and KN-93) had no effect on the rate-dependent changes of twitch force and [Ca2+]i transient kinetics, suggesting that protein kinase A (PKA), protein kinase PKG) and Ca2+-calmodulin-dependent protein kinase II (CaM/kinase II) were not responsible for these kinetic changes. 6. Despite the changes in twitch force and [Ca2+]i transient kinetics, the rate-limiting step for the rate-dependent force relaxation still resides at the level of the contractile proteins. 7. Our results suggest that rate-dependent changes in force and [Ca2+]i transients do not depend on PKA or CaM/kinase II activity but might result from intrinsic features of the contractile and/or Ca2+-handling proteins.

Analysis of Variance↗
PubMed2000

Evaluation of [O-methyl-11C]RS-15385-197 as a positron emission tomography radioligand for central alpha2-adrenoceptors.

Carbon-11 labelled RS-15385-197 and its ethylsulphonyl analogue, RS-79948-197, were evaluated in rats as potential radioligands to image central alpha2-adrenoceptors in vivo. The biodistributions of both compounds were comparable with that obtained in an earlier study using tritiated RS-79948-197 and were consistent with the known localisation of alpha2-adrenoceptors. The maximal signals (total to non-specific binding) were, however, reduced, in the order [11C]RS-79948-197 < [11C]RS-15385-197 < [3H]RS-79948-197, primarily due to the difference in radiolabel position (O-methyl for carbon- 11 compared with S-ethyl for tritium). This resulted in the in-growth of radiolabelled metabolites in plasma, which, in turn, contributed to the non-specific component of brain radioactivity. Nonetheless, the signal ratio of approximately 5 for a receptor-dense tissue compared with the receptor-sparse cerebellum, at 90-120 min after radioligand injection, encouraged the development of [O-methyl-11C]RS-15385-197 for human positron emission tomography (PET). Unfortunately, in two human PET scans (each of 90 min), brain extraction of the radioligand was minimal, with volumes of distribution more than an order of magnitude lower than that measured in rats. Following intravenous injection, radioactivity was retained in plasma and metabolism of the radiolabelled compound was very low. Retrospective measurements of in vitro plasma protein binding and in vivo brain uptake index (BUI) in rats demonstrated a higher protein binding of the radioligand in human compared with rat plasma and a lower BUI in the presence of human plasma. It is feasible that a higher affinity of RS-15385-197 for human plasma protein compared with receptor limited the transport of the radioligand. Although one of the PET scans showed a slight heterogeneity in biodistribution of radioactivity which was consistent with the known localisation of alpha2-adrenoceptors in human brain, it was concluded that [O-methyl-11C]RS-15385-197 showed little promise for routine quantification of alpha2-adrenoceptors in man.

Adult↗
PubMed2000

The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity.

This study identifies by microautoradiography activated microglia/macrophages as the main cell type expressing the peripheral benzodiazepine binding site (PBBS) at sites of active CNS pathology. Quantitative measurements of PBBS expression in vivo obtained by PET and [(11)C](R)-PK11195 are shown to correspond to animal experimental and human post-mortem data on the distribution pattern of activated microglia in inflammatory brain disease. Film autoradiography with [(3)H](R)-PK11195, a specific ligand for the PBBS, showed minimal binding in normal control CNS, whereas maximal binding to mononuclear cells was found in multiple sclerosis plaques. However, there was also significantly increased [(3)H](R)-PK11195 binding on activated microglia outside the histopathologically defined borders of multiple sclerosis plaques and in areas, such as the cerebral central grey matter, that are not normally reported as sites of pathology in multiple sclerosis. A similar pattern of [(3)H](R)-PK11195 binding in areas containing activated microglia was seen in the CNS of animals with experimental allergic encephalomyelitis (EAE). In areas without identifiable focal pathology, immunocytochemical staining combined with high-resolution emulsion autoradiography demonstrated that the cellular source of [(3)H](R)-PK11195 binding is activated microglia, which frequently retains a ramified morphology. Furthermore, in vitro radioligand binding studies confirmed that microglial activation leads to a rise in the number of PBBS and not a change in binding affinity. Quantitative [(11)C](R)-PK11195 PET in multiple sclerosis patients demonstrated increased PBBS expression in areas of focal pathology identified by T(1)- and T(2)-weighted MRI and, importantly, also in normal-appearing anatomical structures, including cerebral central grey matter. The additional binding frequently delineated neuronal projection areas, such as the lateral geniculate bodies in patients with a history of optic neuritis. In summary, [(11)C](R)-PK11195 PET provides a cellular marker of disease activity in vivo in the human brain.

Adult↗
PubMed2000

The multidisciplinary clinic approach to prostate cancer counseling and treatment.

The optimum management for an individual patient with prostate cancer is not well defined. Patients with localized disease may be offered options ranging from observation, hormonal therapy, cryotherapy, radiation therapy, or surgery. Each option may have unique aspects to consider when counseling a patient often leading to multiple physician visits over an extended period of time. Since 1996, the Kimmel Cancer Center of Thomas Jefferson University has offered newly diagnosed urologic cancer patients the opportunity to be evaluated in a multidisciplinary clinic. Here, multiple physician consultative visits, including pathologic and radiologic evaluation and protocol evaluation, are provided during the session. Herein we report on our experience with this multidisciplinary approach for patients with prostate cancer.

Cancer Care Facilities↗
PubMed1999

[11C](R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen's encephalitis.

This study was designed to explore the feasibility of PET using [11C](R)-PK11195 as an in vivo marker of activated microglia/brain macrophages for the assessment of neuroinflammation in Rasmussen's encephalitis (RE). [11C](R)-PK11195 PET was carried out in four normal subjects, two patients with histologically confirmed RE, and three patients with clinically stable hippocampal sclerosis and low seizure frequency. Binding potential maps showing specific binding of [11C](R)-PK11195 were generated for each subject. Regional binding potential values were calculated for anatomically defined regions of interest after coregistration to and spatial transformation into the subjects' own MRI. In one patient with RE who underwent hemispherectomy, the resected, paraffin-embedded brain tissue was stained with an antibody (CR3/43) that labels activated human microglia. Whereas specific binding of [11C](R)-PK11195 in clinically stable hippocampal sclerosis was similar to that in normal brain, patients with RE showed a focal and diffuse increase in binding throughout the affected hemisphere. In RE, [11C](R)-PK11195 PET can reveal in vivo the characteristic, unilateral pattern known from postmortem neuropathologic study. PET imaging of activated microglia/brain macrophages offers a tool for investigation of a range of brain diseases where neuroinflammation is a component and in which conventional MRI does not unequivocally indicate an inflammatory tissue reaction. [11C](R)-PK11195 PET may help in the choice of appropriate biopsy sites and, further, may allow assessment of the efficacy of antiinflammatory disease-modifying treatment.

Adolescent↗
PubMed1999

Assessment of spatial normalization of PET ligand images using ligand-specific templates.

Recent advances allow robust computation of parametric maps of ligand-receptor binding from PET data sets. Parametric maps may be statistically analyzed at the voxel level, given suitable techniques for both the spatial normalization of image data into a standard space and the application of appropriate statistical tests. The purpose of this study was to spatially normalize parametric maps of [carbonyl-11C]WAY-100635 and [11C]raclopride binding using SPM 96 and ligand-specific templates. Ligand-specific templates were created from integral images taken from healthy subjects. For this, a MRI-based spatial normalization was used: T1-weighted MRI scans were coregistered to the PET integral images, and the spatial normalization of the MRI to the SPM 96 T1 MRI template was applied to the integral images. These integral images were meaned and smoothed to form [carbonyl-11C]WAY-100635 and [11C]raclopride templates. Reliability of spatial normalization using the ligand template method and the previous MRI-based spatial normalization was investigated by using a second set of integral images taken from a different cohort: Landmark coordinates were defined on all spatially normalized integral images. Mean coordinates were found in order to produce an overall (average) landmark for each location. For each image, at each location, the distance from the landmark coordinates to the overall landmark were found. A multivariate analysis of variance was used to examine the effects of observer variance, landmark location, and the method used. Visually acceptable templates were created. While observer variance was not significant, the landmark x method interaction was significant. The ligand template method had significantly smaller distances: Among the landmark locations with this method, the mean distances between individual image landmarks and overall image landmarks ranged from 1. 1 to 4.9 mm. The ligand template method provides a reliable approach for spatial normalization of PET ligand images.

Algorithms↗
PubMed1999

The Next Step Trial: impact of a worksite colorectal cancer screening promotion program.

BACKGROUND: The Next Step Trial was a randomized trial of worksite colorectal cancer screening promotion and nutrition interventions for automobile industry employees at increased risk of colorectal cancer. Interventions were tested at 28 worksites with 5,042 employees. This report describes results of the screening promotion intervention. METHODS: Worksites randomized to the control group received a standard program including rectal examination, fecal occult blood testing, and flexible sigmoidoscopy. Intervention worksites received an enhanced program (i.e., standard program plus an educational booklet/telephone call). Compliance (i.e., completion of all recommended screening examinations) and coverage (i.e., completion of at least one screening examination), the primary and secondary outcomes, were measured over 2 years. RESULTS: In the 2 years prior to baseline, 61% of employees had been screened. After random assignment, baseline differences in several employee characteristics and worksite screening procedures were detected, including more past history of screening in control worksites. After adjusting for differences, we found modest, but higher, compliance and coverage in intervention compared with control worksites (odds ratio [95% confidence limits] = 1.46 [1.1-2.0] and 1.33 [1.1, 1.6], respectively). CONCLUSIONS: Adding a personally tailored behavioral intervention to a standard colorectal cancer screening program can promote continued employee participation in screening as measured by compliance. Further research is needed to assess intervention effects in other populations.

Automobiles↗
PubMed1999

Nutrition intervention for high-risk auto workers: results of the Next Step Trial.

BACKGROUND: The Next Step Trial tested interventions encouraging prevention and early detection practices in automotive-industry employees at increased colorectal cancer risk. This article describes results of the nutrition intervention promoting low-fat, high-fiber eating patterns. METHODS: Twenty-eight worksites (5,042 employees at baseline) were randomized to a 2-year nutrition intervention including classes, mailed self-help materials, and personalized dietary feedback. Control worksites received no intervention. Nutrition outcomes were assessed by mailed food frequency questionnaires (FFQs) Primary nutrition outcomes included percentage energy from fat and fiber density (g/1,000 kcal) at 1 year postrandomization. Secondary outcomes included servings of fruits/vegetables and dietary measures at 2 years postrandomization. Analyses were adjusted for within worksite correlations and baseline covariates. Fifty-eight percent of employees returned FFQs. RESULTS: At 1 year, there were modest but statistically significant intervention effects for fat (-0.9 %en), fiber (+0.5 g/1,000 kcal), and fruits/vegetables (+0.2 servings/day) (all P < 0.007). At 2 years, due to significant positive changes in control worksites, intervention effects were smaller, significant for fiber only. Intervention effects were larger in younger (<50 years), active employees and class attendees. CONCLUSION: The nutrition intervention produced significant but modest effects on dietary fat and fiber and fruits/vegetables in these high-risk employees. Age and dose effects suggest younger employees may be more responsive to this intervention.

Adult↗
PubMed1999

Evaluation of biomarker modulation by fenretinide in prostate cancer patients.

An NCI-sponsored, phase II trial of N-(4-hydroxyphenyl)- retinamide (4-HPR) in patients with organ-confined prostate cancer in the period prior to radical prostatectomy was carried out. Thirty-seven men with the histologic diagnosis of prostate cancer planning to have radical prostatectomy entered the study after informed consent and were given 4-HPR (or matching placebo) as a single daily dose (two 100-mg capsules of 4-HPR or two capsules of placebo daily) for 3 weeks prior to surgery. Four men dropped out for unrelated reasons. Thirty-three men completed the study. At the time of surgery, repeat biopsies of the prostate were performed to study the effects of the drug on potential surrogate endpoint biomarkers (SEBs) of malignancy within the tissue. The panel of potential SEBs of malignancy include p53, cytomorphometric indices, ploidy, PNCA, erbB-2, erbB-3, EGF receptor, TGF-alpha tumor-associated glycoprotein-72, fatty acid synthetase and Lewis Y antigen. Twenty-three patients had matching pre- and posttherapy lesions and were considered informative. Results from the patients indicate significant differential expression of biomarkers in pretreatment specimens of uninvolved prostatic tissue (normal-appearing epithelia) prostatic intraepithelial neoplasia (PIN) and prostate cancer. The mean erbB-2 expression was 0.58 in uninvolved vs. 1.04 in PIN (p = 0.002); while the mean erbB-2 expression was 1.35 in prostate cancer (p = 0.0007, uninvolved vs. prostate cancer). A similar pattern of increased biomarker expression between uninvolved and PIN or prostate cancer tissues can be observed for EGF receptor (mean = 1.21, 1.87 and 1.76 for uninvolved, PIN and prostate cancer, respectively) and erbB-3 (mean = 0.81, 1.59 and 1.30 for uninvolved, PIN and prostate cancer, respectively). There were no statistically significant differences in biomarkers observed in the 4-HPR-treated patients when compared with placebo-treated control patients. There was a posttreatment up-regulation of biomarkers observed in both groups of patients. This observation is most likely explained by an effect due to the diagnostic sextant biopsy equally affecting both groups of patients. Results from this study do not demonstrate a chemoprevention effect of 4-HPR on tissue-based SEBs at the dose given.

Adenocarcinoma↗
PubMed1999

Radio-imaging in small animals.

As the resolution of radio-imaging systems improves, the prospect of in-vivo imaging of small animals becomes more attractive. Purpose-built positron emission tomography (PET) scanners capable of imaging individual tissues within the rat brain are now in routine experimental use and in-vivo tracer and saturation-kinetic studies are now possible. The study of small animals in this way does have intrinsic problems and constraints associated with it. For example, the animal must be completely immobilized, stable ligand within the radiolabelled preparation may be limiting and anatomical definition may be poor. In spite of this, consistent, semi-quantitative data can be produced and in-vivo radio-imaging can provide a genuine and unique complement to more conventional techniques. Animal numbers can be significantly reduced and the quality of data improved due to reduced inter-animal variation, and longitudinal studies, to monitor disease progression, are feasible. As the resolution of imaging systems improves still further, such studies could be extended to mouse, in addition to rat, models of disease.

Animals↗