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T Wheeler

Publications and source records attributed to T Wheeler.

At least 19 recordsLinked to original sources
PubMed2001

Web-based tissue microarray image data analysis: initial validation testing through prostate cancer Gleason grading.

Tissue microarray technology promises to enhance tissue-based molecular research by allowing improved conservation of tissue resources and experimental reagents, improved internal experimental control, and increased sample numbers per experiment. Organized, well-validated collection and analysis of the voluminous image data produced by tissue microarray technology is critical to maximize its value. Web-based technology for visual analysis and searchable storage of microarray image data could provide optimal flexibility for research groups in meeting this goal, but this approach has not been examined scientifically. Toward this goal, a prostate tissue microarray block containing 432 tissue cores (0.6 mm diameter) was constructed. Moderately compressed (200 kb).jpg images of each tissue spot were acquired and were saved using a naming convention developed by the SPORE Prostate Tissue Microarray Collaborative Group. Four hundred three tissue array spot images were uploaded into a database developed for this study and were converted to.fpx format to decrease Internet transmission times for high-resolution image data. In phase I of the image analysis portion of the study, testing and preliminary analysis of the Web technology was performed by 2 pathologists (M.A.R. and G.S.B.). In phase II, 2 pathologists (J.I.E. and T.M.W.) with no previous exposure to this technology and no knowledge of the structure of the study were presented a set of 130 sequential tissue spot images via the Web on their office computers. In phase III, the same pathologists were presented a set of 193 images, including all 130 from phase II and 63 others, with image presentation order randomized. With each zoomable tissue spot image, each pathologist was presented with a nested set of questions regarding overall interpretability of the image, presence or absence of cancer, and predominant and second most frequent Gleason grade. In phases II and III of the study, 319 of 323 (99%) image presentations using this Web technology were rated interpretable. Comparing the 2 pathologists' readings in phases II and III, Gleason grade determinations by each pathologist were identical in 179 of 221 (81%) determinations and were within 1 point of each other in 221 of 221 (100%) determinations, a performance rate similar to if not better than that previously reported for direct microscopic Gleason grading. Interobserver comparison of Gleason score determinations and intraobserver comparisons for Gleason grade and score also showed a pattern of uniformity similar to those reported in direct microscope-based Gleason grading studies. Interobserver (7.5%) and intraobserver (5% and 3%) variability in determining whether diagnosable cancer was present point out the existence of a "threshold effect" that has rarely been studied but may provide a basis for identification of features that are most amenable to improved diagnostic standardization. In summary, storage and analysis of tissue microarray spot images using Web-based technology is feasible and practical, and the quality of images obtained using the techniques described here appears adequate for most tissue-based pathology research applications. HUM PATHOL 32:417-427.

Databases, Factual↗
PubMed2001

Maternal plasma vascular endothelial growth factor concentrations in normal and hypertensive pregnancies and their relationship to peripheral vascular resistance.

OBJECTIVE: The aim of this study was to measure maternal plasma vascular endothelial growth factor concentrations during normal and hypertensive pregnancies and examine their relationship with maternal total peripheral resistance values. STUDY DESIGN: Plasma concentrations of total immunoreactive vascular endothelial growth factor and total peripheral resistances were measured serially throughout pregnancy in 20 women with preeclampsia, 24 women with gestational hypertension, and 26 normotensive control women. One-way analysis of variance and a regression model were used to analyze the vascular endothelial growth factor levels in the groups and the relationship between vascular endothelial growth factor concentration and total peripheral resistance. RESULTS: At 10 to 14 weeks' gestation plasma vascular endothelial growth factor concentrations in all subjects were 4 to 5 times greater than the levels measured post partum (P <.0001). Mean vascular endothelial growth factor concentrations were similar in the control and gestational hypertension groups; in both groups levels remained stable until 34 to 36 weeks' gestation, when levels increased a further 1.3-fold (P <.01). In comparison, vascular endothelial growth factor concentrations in subjects in the preeclampsia group were greater at 28 to 32 weeks' gestation (P =.002) and at 34 to 36 weeks' gestation (P <.001). Vascular endothelial growth factor concentrations were also increased during the 4 weeks that preceded the diagnosis of preeclampsia (P <.05). Vascular endothelial growth factor concentrations were associated with the elevated total peripheral resistance observed during the clinical disorder in the preeclampsia group but not in the other groups. CONCLUSION: Maternal plasma vascular endothelial growth factor concentrations increased before the clinical onset of preeclampsia and were further elevated during the vasoconstricted state observed in this disorder. We speculate that the hyperdynamic circulation that characterizes the latent phase of preeclampsia causes vascular shear stress, which in turn increases the levels of circulating vascular endothelial growth factor. Because vascular endothelial growth factor normally acts as a vasodilator, its increase may represent an unsuccessful vascular rescue response.

Adult↗
PubMed2001

Development, analysis, refinement, and utility of an interdisciplinary amyotrophic lateral sclerosis database.

The current status of evaluation and management provided by individual healthcare professionals (HCP) at amyotrophic lateral sclerosis (ALS) centers and clinics needs to be analyzed. This paper describes one ALS center's experiences with the development, analysis, refinement, and utility of an interdisciplinary, HCP-driven ALS database. The purpose and conceptual framework of the database, the general data that needed to be collected, and the types of reports that needed to be generated were determined, and, in collaboration with a computer programmer, data entry and database management systems were developed. Data were collected on 234 patients between September 1996 and August 1998, and were analyzed by a biostatistician. Based on review of the biostatistician's report and discussion of problems encountered with the systems, the database was then refined. Benefits of the database system included: systematization of data collection and reporting, reduction of redundant data collection by individuals, decreased variability of evaluation methods and management decisions from patient to patient, and increased availability of a variety of uniform patient information to assist team members in making care decisions. Ongoing refinement will ensure that this HCP-driven ALS database continues to be informative, practical and effective for decision-making and enhancing delivery of care.

Adult↗
PubMed2001

Bilateral nerve graft during radical retropubic prostatectomy: 1-year followup.

PURPOSE: With the interposition of a sural nerve graft to replace resected cavernous nerves at radical retropubic prostatectomy, we have previously reported the return of effective erectile function. We determine the efficacy of this procedure in a series of men with at least 1-year followup. MATERIALS AND METHODS: A total of 12 potent men (mean age plus or minus standard deviation 57 +/- 6 years) with clinically localized prostate cancer underwent radical retropubic prostatectomy, with deliberate wide bilateral neurovascular bundle resection and placement of bilateral nerve grafts. A series of patient and partner erectile dysfunction questionnaires, and patient interviews were performed at 3, 6, 12 and 18 months postoperatively. Only results for those men with a followup of 12 months or greater (mean 16 +/- 4) are presented. A control group of 12 men who had undergone bilateral nerve resection but declined nerve graft placement, was also followed. RESULTS: Of the 12 men 4 (33%) had spontaneous medically unassisted erections sufficient for sexual intercourse with vaginal penetration. An additional 5 (42%) men describe "40 to 60%" spontaneous erections, with fullness, no rigidity and not able to penetrate. Overall, 9 (75%) men had return of erectile activity. No demonstrable erections occurred before 5 months postoperatively. The greatest return of function was observed at 14 to 18 months after surgery. CONCLUSIONS: This surgical technique has minimal morbidity and represents a significant advance in prostate cancer surgery in men requiring bilateral nerve resection. Our study clearly demonstrates recovery of erectile function in men who underwent bilateral nerve graft placement during radical retropubic prostatectomy when both cavernous nerves were deliberately resected.

Aged↗
PubMed2001

Neonatal bone mass: influence of parental birthweight, maternal smoking, body composition, and activity during pregnancy.

Evidence is accumulating that intrauterine growth and development may influence an individual's risk of osteoporosis in later adult life. To examine maternal and paternal influences on intrauterine skeletal growth, we used dual-energy X-ray absorptiometry to measure the neonatal bone mineral content (BMC) and bone mineral density (BMD) of 145 infants born at term. Independently of the infant's duration of gestation at birth, the birthweights of both parents and the height of the father were positively correlated with neonatal whole body BMC. Women who smoked during pregnancy had infants with a lower whole body BMC and BMD; overall, there was a 7.1-g (11%) average difference between whole body BMC of infants whose mothers did and did not smoke during pregnancy (p = 0.005). Women with thinner triceps skinfold thicknesses (reflecting lower fat stores) and those who reported a faster walking pace and more frequent vigorous activity in late pregnancy also tended to have infants with a lower BMC and BMD (p values for BMC; 0.02, 0.03, and 0.05, respectively). Maternal thinness and faster walking pace but not maternal smoking or parental birthweight also were associated with lower bone mineral apparent density (BMAD). The influences on skeletal growth and mineralization were independent of placental weight, a marker of the placental capacity to deliver nutrients to the fetus. These observations point to a combination of genetic and intrauterine environmental influences on prenatal skeletal development and suggest that environmental modulation, even at this early stage of life, may reduce the risk of osteoporosis in adulthood.

Absorptiometry, Photon↗
PubMed2000

Epidemiologic determinants of clinically relevant prostate cancer.

While tumor volume and Gleason scores are the best available prognostic indicators for prostate cancer, contemporary predictive methods are unable to identify which men with Gleason scores of 7 have clinically insignificant tumors that will not progress and which men will develop highly aggressive prostate cancer. Our objective was to evaluate potential environmental determinants of significant prostate cancer. Subjects were patients identified from a university-based hospital and tertiary cancer center who had undergone radical prostatectomy for prostate cancer. Cases were 103 patients whose tumor volumes were </=0.5 ml. The comparison group was comprised of 225 men with larger-volume disease or with histologic evidence of extracapsular extension but without lymph node involvement. The matching criteria were ethnicity, age at diagnosis (+/-5 years), and date of diagnosis (+/-1 year). Epidemiologic data, current weight, and height were obtained. The comparison group was significantly more likely than cases to be current smokers (7.6% vs. 3.9%) and to report more pack-years smoked (30.1 vs. 23.0 years, p = 0.06). Cases tended to weigh less (85.2 vs. 87.1 kg, p = 0.1) and have lower body mass indices (26.8 vs. 27.6, p = 0.07). A similar trend was evident for weight at age 40 (79 vs. 81 kg). Cases reported a mean weight gain of 4.9 kg compared with 6. 6 kg in the comparison subjects (p = 0.05) between the ages of 25 and 40. There was no significant difference in weight gain from age 40 to current age. Cases were more likely to report having prostate cancer screening (90% vs. 80%, p = 0.02). Cases with Gleason scores </=7 (3 + 4, with 3 being the dominant grade) were younger at diagnosis than those with scores of 7 (4 + 3, with 4 being the dominant grade), were more likely (93%) to have had prostate screening, were less likely to be current smokers (4%), reported the fewest pack-years smoked (21.5 vs. 28.6 years for high-score cases and 30.1 for comparison subjects), and had the lowest average weight gain from ages 25 to 40 (4.62 vs. 6.31 kg for high-score cases). Weight gain in early adulthood and smoking thus appear to be important predictors of virulent prostate cancer. Our data also suggest that prior screening is associated with diagnosis of lower-volume and lower-score disease.

Age Factors↗
PubMed2000

Phylogeography of the Caribbean rock iguana (Cyclura): implications for conservation and insights on the biogeographic history of the West Indies.

The Caribbean rock iguana, Cyclura, has had an unstable intrageneric taxonomy and an unclear phylogenetic position within the family Iguanidae. We use mtDNA sequence data to address these issues and explore the phylogeographic history of the genus. ND4 to leucine tRNA sequence data were collected from multiple individuals of each of the eight species of Cyclura (including 15 of 16 subspecies) and from four localities of Iguana iguana (representative of this species' broad geographic range). This data set was combined with sequence data from Sites et al. (1996, Mol. Biol. Evol. 13, 1087-1105) and analyzed under maximum-parsimony and maximum-likelihood optimization criteria. The ND4 region provided good resolution for the majority of nodes, as indicated by high bootstrap support. In agreement with several recent molecular studies, Cyclura is recovered as monophyletic and is not closely related to any other genus, whereas Iguana is strongly supported as the sister taxon to Sauromalus. This result is statistically more likely than other published hypotheses of Iguanid relationships. Cyclura shows a southeast to northwest speciation sequence in the Caribbean, with the most ancient lineage on the Puerto Rican Bank. The amount of interspecific sequence divergence within Cyclura (maximum 11.4%) is very high in comparison to data from other iguanid taxa at this locus, suggesting that this group either has been in the Caribbean for a very long time or has gone through a very rapid rate of evolution at this locus. Using dates from other published studies, we calculate a molecular clock that suggests that Cyclura colonized the Caribbean between 15 and 35 mya. Several questions regarding subspecific taxonomy are raised in the analysis and await further investigation using a more rapidly evolving marker such as nuclear microsatellites.

Animals↗
PubMed2000

Spiritual well-being of the individual with amyotrophic lateral sclerosis.

BACKGROUND: A study was conducted to: (1) establish the feasibility and reliability of the Spiritual Well-Being Scale (SWBS) and its religious (RWB) and existential well-being (EWB) subscales in a sample of individuals with ALS; (2) describe the spiritual and religious practices, and spiritual well-being in these individuals; and (3) examine the relationship between spiritual well-being and quality of life. METHOD: A random sample of 60 individuals completed the SWBS at the beginning and end of an ALS clinic visit. Subjects were classified into early, middle or late stage of ALS, using vital capacity and total ALS Functional Rating Scale scores. A subsample completed the Sickness Impact Profile (SIP). RESULTS: The SWBS and its RWB and EWB subscales were found to have high internal consistency and test-retest reliability. There were no statistically significant differences in SWB, RWB or EWB scores among the three stages of ALS. RWB scores were significantly higher than EWB scores overall and within the middle and late stages. Strong negative correlations were found between physical and psychosocial dimension SIP subscores and RWB scores, suggesting that religious well-being may impact quality of life, or vice versa.

Attitude to Health↗
PubMed1999

Dual anterior interventricular arteries.

A patient with dual left anterior descending (R. interventricularis anterior of the left coronary artery) coronary artery is presented. A normally arising left anterior descending was hypoplastic, and an anomalous left anterior descending, which arose from the right sinus aorticus had a normal caliber. The anomalous left anterior descending artery traversed between the aorta and the pulmonary artery supplying most of the anterior myocardial wall of the left ventricle. This rare coronary anomaly can potentially have implications on percutaneous coronary interventions or on surgical revascularization procedures.

Angioplasty, Balloon, Coronary↗
PubMed1999

Pitfalls in myocardial perfusion assessment with dynamic MR imaging after administration of a contrast material bolus in dogs.

RATIONALE AND OBJECTIVES: The authors evaluated the artifacts observed on myocardial perfusion curves derived from an inversion-prepared fast gradient-echo (GRE) imaging sequence in dogs after injection of a gadolinium-based contrast agent. MATERIALS AND METHODS: Six mongrel dogs were divided into three groups. In groups 1 and 2, anesthesia was maintained with pentobarbital. Group 2 also received an intravenous injection of atropine (0.03 mg/kg). In group 3, anesthesia was maintained with isoflurane (1.0%). Imaging was performed on a 1.5-T magnetic resonance (MR) imaging unit (one section per heart beat, a 30 x 15-cm field of view, 10-mm section thickness, and 64-kHz bandwidth). Region-of-interest (ROI) markers were placed on the blood pool of the left intraventricular cavity, anterior wall of the left ventricle, and anterior to the chest wall to track respiratory motion. RESULTS: In group 1, the signal intensity (SI) periodically increased during each inspiration due to respiratory sinus arrhythmia. The relation between the SI increase and the variation of the delay between images was demonstrated in vitro and by computer simulations. No periodic increase of the SI was observed when regular cardiac rhythm was maintained by pharmacologic inhibition of the vagal-mediated chronotropic response with either the addition of atropine to pentobarbital or the use of isoflurane as the anesthetic agent. CONCLUSION: In an inversion-prepared fast GRE sequence, respiratory sinus arrhythmia can induce periodic SI increase by varying the respiratory rate interval and delay between images.

Animals↗
PubMed1999

Evidence to support a change in follow-up policy for patients with breast cancer: time to first relapse and hazard rate analysis.

The ideal follow-up for patients with cancer should be sensitive to the likelihood of relapse, for prompt investigation and treatment if indicated, together with the support of patient confidence. The current British Association of Surgical Oncologists guidelines for patients with breast cancer suggest intensive follow-up, including 3-monthly clinic visits during the first 2 years. These recommendations place increasing demands on clinical resources. The combined outcome of screening, early detection, dedicated clinical services that emphasize rapid diagnosis and concomitant improved survival, have resulted in increasing absolute numbers of diagnosed breast cancer patients in follow-up clinics. This article examines the follow-up of breast cancer patients to determine if the convention should be adjusted to obtain more from current resources while maintaining equivalent patient care. The data on all patients with breast cancer attending one general oncology clinic were examined in order to determine the pattern of relapse. Analyses identified: (1) the time to relapse at any site and at specific sites; and (2) the prognostic significance of three factors for subsequent relapse, namely nodal status, menopausal status and T stage at diagnosis. In 416 consecutive patients, the annual rate of relapse of breast cancer was found to increase progressively over the first 4 years. Nodal disease was the most important single variable as a predictor of relapse. The annual hazard rate for relapse for node positive patients in the first year was 5%; this increased to 10% and 14% in years three and four respectively. In contrast, in those patients who were node negative at diagnosis (302/416; 73%), the hazard rate for relapse was 1% in year one, increasing to 5% in years three and four. Intensive early follow-up of breast cancer patients provides no clear clinical gain for the great majority of patients, since early relapse is rare in the first year. The use of clinical funds and staff resources might be optimized to focus clinical follow-up on those patients at risk of recurrence. We suggest that all patients should continue to be monitored and receive psychological care through access to their general practitioner, skilled breast care nurses and specialized counsellors. Any patient at risk, or developing symptoms of relapse, would have immediate clinical access to the oncologist for diagnostic investigations. This strategy would optimize psychological patient care and use the full backup of clinical resources during the prolonged period over which relapse becomes more probable.

Adult↗
PubMed1999

Relationship between maternal serum vascular endothelial growth factor concentration in early pregnancy and fetal and placental growth.

Vascular endothelial growth factor (VEGF) has important effects on endothelial cells increasing cell proliferation, permeability and nitric oxide production; concentrations of VEGF in the maternal serum increase during the first 10 weeks of pregnancy. In this study, the relationship of maternal serum VEGF with maternal health during pregnancy and with fetal and placental size at mid-pregnancy and at term was investigated. Serum was obtained from 539 Caucasian women with singleton pregnancies between 8 and 20 weeks of pregnancy (mean 14 weeks). Total serum VEGF concentrations were measured by direct competitive radioimmunoassay. Fetal size and placental volume were measured by ultrasound between 16 and 20 weeks gestation. Birthweight, placental weight and anthropometric measurements of the baby were obtained after delivery. Serum VEGF concentrations were found to be higher in women with a lower weight before pregnancy (P = 0.01) and in those carrying a female fetus (P = 0.002). VEGF concentrations were positively correlated with placental volume (r = 0.17, P = 0.0001) but not with fetal size between 16 and 20 weeks gestation. Serum VEGF concentrations were positively correlated with both birthweight (r = 0.10, P = 0.02) and placental weight at delivery (r = 0.13, P = 0.003). The data presented support the view that VEGF may be one of the factors involved in mediating the maternal cardiovascular adaptation to pregnancy.

Adolescent↗
PubMed1999

Smile for the camera: telemedicine comes to your local dentist's office.

Dentistry has faced the same access issues that have spurred telemedicine development in other fields. However, until recently dentistry has lagged behind in adopting telemedicine. The findings of the Association of Telemedicine Service Provider's (ATSP; www.atsp.org) 1998 Report on US Telemedicine Activity, done collaboratively with Telemedicine Today Magazine, are instructive. Of over 40,000 teleconsults among 139 U.S. programs performed in 1997, only 200 were dental teleconsults--all done by one program. Although that figure represents a significant increase over the 4 dental teleconsults reported in 1996, teledentistry has a long way to go. The first steps are now being taken. At the schools of dentistry at the University of California at Los Angeles and the University of Bristol in Bristol, England, two different approaches to teledentistry are being actively explored. Telemedicine Today spoke with lead researchers at each school to discuss these programs.

England↗
PubMed1998

The transcription factor AP-1 is required for EGF-induced activation of rho-like GTPases, cytoskeletal rearrangements, motility, and in vitro invasion of A431 cells.

Human squamous cell carcinomas (SCC) frequently express elevated levels of epidermal growth factor receptor (EGFR). EGFR overexpression in SCC-derived cell lines correlates with their ability to invade in an in vitro invasion assay in response to EGF, whereas benign epidermal cells, which express low levels of EGFR, do not invade. EGF-induced invasion of SCC-derived A431 cells is inhibited by sustained expression of the dominant negative mutant of c-Jun, TAM67, suggesting a role for the transcription factor AP-1 (activator protein-1) in regulating invasion. Significantly, we establish that sustained TAM67 expression inhibits growth factor-induced cell motility and the reorganization of the cytoskeleton and cell-shape changes essential for this process: TAM67 expression inhibits EGF-induced membrane ruffling, lamellipodia formation, cortical actin polymerization and cell rounding. Introduction of a dominant negative mutant of Rac and of the Rho inhibitor C3 transferase into A431 cells indicates that EGF-induced membrane ruffling and lamellipodia formation are regulated by Rac, whereas EGF-induced cortical actin polymerization and cell rounding are controlled by Rho. Constitutively activated mutants of Rac or Rho introduced into A431 or A431 cells expressing TAM67 (TA cells) induce equivalent actin cytoskeletal rearrangements, suggesting that the effector pathways downstream of Rac and Rho required for these responses are unimpaired by sustained TAM67 expression. However, EGF-induced translocation of Rac to the cell membrane, which is associated with its activation, is defective in TA cells. Our data establish a novel link between AP-1 activity and EGFR activation of Rac and Rho, which in turn mediate the actin cytoskeletal rearrangements required for cell motility and invasion.

Actins↗
PubMed1998

Quantification of myocardial perfusion by MRI after coronary occlusion.

The objectives of this study were to define the relationship between the first order constant of Gd-DTPA transfer (K1) and the myocardial blood flow (MBF) at rest and to compare it with an equivalent relationship obtained for positron emission tomography (PET). In a canine model of permanent coronary occlusion (n = 4), myocardial and blood time concentration curves obtained by 13N-ammonia PET and Gd-DTPA-enhanced MRI were fitted by a one-compartment model to determine K1. A linear relationship was observed between MRI-derived K1 and MBF measured by microspheres (K1 = 0.88 x flow -0.015, R = 0.95), which compares favorably with the equivalent relationship derived from PET (K1 = 0.74 x flow +0.16, R = 0.88). The results of this preliminary study suggest that, at rest and distal to a permanently occluded coronary artery, myocardial perfusion quantification by MRI is possible and can challenge PET.

Animals↗
PubMed1998

A longitudinal study of maternal serum vascular endothelial growth factor in early pregnancy.

Using a competitive radioimmunoassay to measure total immunoreactive vascular endothelial growth factor (VEGF), we describe for the first time longitudinal changes in serum VEGF in early pregnancy. The measurements were obtained from 26 women following the transfer of cryopreserved embryos; 18 singleton and eight twin pregnancies were identified by ultrasound at 6 weeks gestation and subsequently delivered as live births. Subjects did not have corpora lutea and exogenous hormone support was provided for the first 70 days of pregnancy. Serum VEGF increased approximately 30 days after embryo transfer and thereafter continued to rise in both singleton and twin pregnancies over a period of 20-40 days after which concentrations remained elevated. The longitudinal profile of serum VEGF concentrations was characterized by a logistic curve for singleton and twin pregnancies; the profile of VEGF concentrations in the twin pregnancies was significantly higher than in the singleton pregnancies (P < 0.0001). Profiles of the longitudinal concentrations of serum human chorionic gonadotrophin (HCG), oestradiol and progesterone were created by polynomial regression for singleton and twin pregnancies. The VEGF profiles were positively correlated with the profiles of HCG (r = 0.44, P = 0.02) and oestradiol (r = 0.36, P = 0.07) but not progesterone (r = 0.16, P = 0.42). Serum VEGF concentrations in the singleton thawed embryo pregnancies were compared with gestation-matched normal singleton pregnancies with corpora lutea. Concentrations of VEGF were significantly (P = 0.004) greater in the pregnancies with corpora lutea although this difference became less marked with advancing gestation. In addition to its important role in angiogenesis, we speculate that VEGF is involved in mechanisms which control the maternal cardiovascular adaptation to pregnancy.

Chorionic Gonadotropin↗