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Biomedical subjects

E C Nelson

Publications and source records attributed to E C Nelson.

At least 19 recordsLinked to original sources
PubMed2006

Clinical implications of neuroendocrine differentiation in prostate cancer.

The cellular signaling pathways of the prostate play a central role in the induction, maintenance, and progression of prostate cancer (CaP). Neuroendocrine (NE) cells demonstrate attributes that suggest they are an integral part of these signaling cascades. We summarize what is known regarding NE cells in CaP focusing on NE cellular transdifferentiation. This significant event in CaP progression appears to be accelerated by androgen deprivation (AD) treatment. We examine biochemical pathways that may impact NE differentiation in a chronological manner focusing on AD therapy (ADT) as a central event in inducing androgen-independent CaP. Our analysis is limited to the common adenocarcinoma pattern of CaP and excludes small-cell and carcinoid prostatic variants. In conclusion, we speculate on the future of treatment and research in this area.

Adenocarcinoma↗
PubMed2003

Outer membrane protein alterations and blaTEM-1 variants: their role in beta-lactam resistance in Klebsiella pneumoniae.

OBJECTIVES: The aim of the study was to characterize the genetic basis of resistance to selected beta-lactam antibiotics in two clinical isolates of Klebsiella pneumoniae. METHODS AND RESULTS: K. pneumoniae strains were isolated from two hospitalized patients. One of the strains was resistant to amoxicillin, co-amoxiclav, cefuroxime, piperacillin and cefoxitin but susceptible to all the other cephalosporins tested. The second strain displayed a similar phenotype except that it was resistant to piperacillin/tazobactam and susceptible to cefoxitin. PCR assays and DNA sequencing showed that the cefoxitin-susceptible strain contained a novel blaTEM-1 variant downstream of the strong Pa/Pb promoter. SDS-PAGE analysis of the outer membrane proteins (OMPs) did not identify OmpK35 and suggested reduced expression of OmpK36 in this strain. Following passage in non-selective media, expression of OmpK36 was restored with a concomitant increase in cefuroxime susceptibility. A similar experimental approach identified blaTEM-1C in the cefoxitin-resistant K. pneumoniae strain. This strain was deficient in OmpK35 and OmpK36; absence of the latter protein was due to the presence of IS1 in the ompK36 regulatory region. CONCLUSIONS: Resistance to selected beta-lactams in two clinical isolates of K. pneumoniae was due to interplay between the expression of OMPs and TEM-1.

Anti-Bacterial Agents↗
PubMed2002

A twin study of genetic and environmental influences on suicidality in men.

BACKGROUND: Previous studies that have examined genetic influences on suicidal behaviour were confounded by genetic vulnerability for psychiatric risk factors. The present study examines genetic influences on suicidality (i.e. suicidal ideation and/or suicide attempt) after controlling for the inheritance of psychiatric disorders. METHODS: Sociodemographics, combat exposure, lifetime DSM-III-R major depression, bipolar disorder, childhood conduct disorder, adult antisocial personality disorder, panic disorder, post-traumatic stress disorder, drug dependence, alcohol dependence and lifetime suicidal ideation and attempt were assessed in 3372 twin pairs from the Vietnam Era Twin Registry who were assessed in 1987 and 1992. Genetic risk factors for suicidality were examined in a multinomial logistic regression model. Additive genetic, shared environmental and non-shared environmental effects on suicidality were estimated using structural equation modelling, controlling for other risk factors. RESULTS: The prevalence of suicidal ideation and suicide attempt were 16.1% and 2.4% respectively. In a multinomial regression model, co-twin's suicidality, being white, unemployment, being other than married, medium combat exposure and psychiatric disorders were significant predictors for suicidal ideation. Co-twin's suicidality, unemployment, marital disruption, low education attainment and psychiatric disorders (except childhood conduct disorder) were significant predictors for suicide attempt. Model-fitting suggested that suicidal ideation was influenced by additive genetic (36%) and non-shared environmental (64%) effects, while suicide attempt was affected by additive genetic (17%), shared environmental (19%) and non-shared environmental (64%) effects. CONCLUSIONS: There may be a genetic susceptibility specific to both suicidal ideation and suicide attempt in men, which is not explained by the inheritance of common psychiatric disorders.

Adult↗
PubMed2002

Genetic and environmental contributions to cannabis dependence in a national young adult twin sample.

BACKGROUND: This paper examines genetic and environmental contributions to risk of cannabis dependence. METHOD: Symptoms of cannabis dependence and measures of social, family and individual risk factors were assessed in a sample of 6265 young adult male and female Australian twins born 1964-1971. RESULTS: Symptoms of cannabis dependence were common: 11.0% of sample (15.1% of men and 7.8% of women) reported two or more symptoms of dependence. Correlates of cannabis dependence included educational attainment, exposure to parental conflict, sexual abuse, major depression, social anxiety and childhood conduct disorder. However, even after control for the effects of these factors, there was evidence of significant genetic effects on risk of cannabis dependence. Standard genetic modelling indicated that 44.7% (95% CI = 15-72.2) of the variance in liability to cannabis dependence could be accounted for by genetic factors, 20.1% (95% CI = 0-43.6) could be attributed to shared environment factors and 35.3% (95% CI = 26.4-45.7) could be attributed to non-shared environmental factors. However, while there was no evidence of significant gender differences in the magnitude of genetic and environmental influences, a model which assumed both genetic and shared environmental influences on risks of cannabis dependence among men and shared environmental but no genetic influences among women provided an equally good fit to the data. CONCLUSIONS: There was consistent evidence that genetic risk factors are important determinants of risk of cannabis dependence among men. However, it remains uncertain whether there are genetic influences on liability to cannabis dependence among women.

Adult↗
PubMed2001

Sub-Angstrom high-resolution transmission electron microscopy at 300 keV.

Sub-Angstrom transmission electron microscopy has been achieved at the National Center for Electron Microscopy (NCEM) by a one-Angstrom microscope (OAM) project using software and enhanced hardware developed within a Brite-Euram project (Ultramicroscopy 64 (1996) 1). The NCEM OAM provides materials scientists with transmission electron microscopy at a resolution better than 1 A by using extensive image reconstruction to exploit the significantly higher information limit of an FEG-TEM over its Scherzer resolution limit. Reconstruction methods chosen used off-axis holograms and focal series of underfocused images. Measured values of coherence parameters predict an information limit of 0.78 A. Images from a [1 1 0] diamond test specimen show that sub-Angstrom resolution of 0.89 A has been achieved with the OAM using focal series reconstruction.

Journal Article↗
PubMed2001

Increasing understanding of patient needs during and after hospitalization.

BACKGROUND: The value of patient satisfaction surveys in health care improvement remains controversial. This study examined the value of alternative ways of identifying patient needs and estimating importance of those needs in improving the impact of satisfaction surveys. METHODS: Ninety-one acute myocardial infarction (AMI) patients from three southeast U.S. community hospitals were surveyed in 1992. Critical incident and person-focused interviews were used to identify patient needs. Besides overall/global satisfaction with care, patients rated satisfaction with and importance of 12 care delivery and 18 information and support needs. Unmet need scores (importance minus satisfaction) were estimated. Derived importance scores were assessed by correlating global satisfaction with individual need satisfaction scores. A two-step process for identifying priority areas for improvement was proposed. RESULTS: Patients identified and assigned greater scores to unmet needs for information and support needs (not included in typical satisfaction surveys) compared to typically assessed care delivery needs (p < 0.0001). Direct importance ratings differed substantially from those derived through correlation analyses (r = 0.28, p > 0.3 for care delivery needs and r = -0.17, p > 0.4 for information and support needs). Needs that received high importance and low satisfaction scores were all information and support needs. DISCUSSION: Needs that patients consider very important are usually ignored in typical patient surveys. Derived approaches typically used to assess importance of need from satisfaction data may provide misleading results. If satisfaction surveys are to result in real performance improvement, a fresh examination of the content and importance assessment strategies, as proposed, is needed.

Adult↗
PubMed2001

Suicide attempts in an adolescent female twin sample.

OBJECTIVE: To examine suicide attempts in an epidemiologically and genetically informative youth sample. METHOD: 3,416 Missouri female adolescent twins (85% participation rate) were interviewed from 1995 to 2000 with a telephone version of the Child Semi-Structured Assessment for the Genetics of Alcoholism, which includes a detailed suicidal behavior section. Mean age was 15.5 years at assessment. RESULTS: At least one suicide attempt was reported by 4.2% of the subjects. First suicide attempts were all made before age 18 (and at a mean age of 13.6). Major depressive disorder, alcohol dependence, childhood physical abuse, social phobia, conduct disorder, and African-American ethnicity were the factors most associated with a suicide attempt history. Suicide attempt liability was familial, with genetic and shared environmental influences together accounting for 35% to 75% of the variance in risk. The twin/cotwin suicide attempt odds ratio was 5.6 (95% confidence interval [CI] 1.75-17.8) for monozygotic twins and 4.0 (95% CI 1.1 -14.7) for dizygotic twins after controlling for other psychiatric risk factors. CONCLUSIONS: In women, the predisposition to attempt suicide seems usually to manifest itself first during adolescence. The data show that youth suicide attempts are familial and possibly influenced by genetic factors, even when controlling for other psychopathology.

Adolescent↗
PubMed2001

Predictors of non-response to a questionnaire survey of a volunteer twin panel: findings from the Australian 1989 twin cohort.

Questionnaire surveys, while more economical, typically achieve poorer response rates than interview surveys. We used data from a national volunteer cohort of young adult twins, who were scheduled for assessment by questionnaire in 1989 and by interview in 1996-2000, to identify predictors of questionnaire non-response. Out of a total of 8536 twins, 5058 completed the questionnaire survey (59% response rate), and 6255 completed a telephone interview survey conducted a decade later (73% response rate). Multinomial logit models were fitted to the interview data to identify socioeconomic, psychiatric and health behavior correlates of non-response in the earlier questionnaire survey. Male gender, education below University level, and being a dizygotic rather than monozygotic twin, all predicted reduced likelihood of participating in the questionnaire survey. Associations between questionnaire response status and psychiatric history and health behavior variables were modest, with history of alcohol dependence and childhood conduct disorder predicting decreased probability of returning a questionnaire, and history of smoking and heavy drinking more weakly associated with non-response. Body-mass index showed no association with questionnaire non-response. Despite a poor response rate to the self-report questionnaire survey, we found only limited sampling biases for most variables. While not appropriate for studies where socioeconomic variables are critical, it appears that survey by questionnaire, with questionnaire administration by telephone to non-responders, will represent a viable strategy for gene-mapping studies requiring that large numbers of relatives be screened.

Adult↗
PubMed2001

Obsessive-compulsive scale of the child behavior checklist: specificity, sensitivity, and predictive power.

OBJECTIVE: To create an obsessive-compulsive disorder subscale (OCS) of the Child Behavior Checklist (CBCL) and to determine its internal consistency, sensitivity, specificity, and positive and negative predictive power to identify obsessive-compulsive disorder (OCD) in children and adolescents. METHODS: Three samples of equal size (n = 73) of children and adolescents, matched for age, gender, and race, were selected for these analyses: 1) a clinically ascertained OCD group, 2) a psychiatrically treated group whose records revealed no evidence of OCD, and 3) a general population control group. An OCS was created by applying factor analysis to 11 CBCL items. Examinations of internal consistency, sensitivity, specificity, and positive and negative predictive value were undertaken. RESULTS: Of 11 items hypothesized to predict OCD, 8 items were retained after factor analyses (smallest factor loading: 0.49) and used to calculate OCS scores. The retained items displayed excellent internal consistency (Cronbach's alpha coefficient = 0.84). OCD participants had significantly higher OCS scores than either psychiatrically treated or general population control groups. With the use of the 2 cutoff scores closest to the true rate of OCD in the overall sample, sensitivity was 75.3% to 84.9%, specificity was 82.2% to 92.5%, positive predictive value was 70.5% to 83.3%, and negative predictive value was 88.2% to 91.6%. CONCLUSION: The performance of the proposed CBCL OCS compares favorably with that of the only previously studied screening instrument for OCD, the Leyton Obsessional Inventory-Child Version. Unlike the Leyton Obsessional Inventory-Child Version, the CBCL is already in widespread use as a screen for most other forms of psychopathology. As the performance of the CBCL OCS will need to be replicated in other sample populations, data with various cutoff levels are provided to enable investigators and clinicians to tailor its use to specific study populations.

Adolescent↗
PubMed2001

Patrick Browne M. D. (c. 1720-1790), an Irish doctor in the Caribbean: his residence on Saint Croix (1757-1765) and his unpublished accounts of volcanic activity on Montserrat.

Patrick Browne resided on the Caribbean islands of Saint Croix (a Danish possession) and Montserrat (an English possession) during the 1750s and 1760s. He collected and recorded the flora of Saint Croix; some of his notes about the plants of the island have survived and are transcribed. On Montserrat he made observations on the active volcano; the surviving manuscript accounts of the sulphur-rich springs are transcribed.

History, 18th Century↗
PubMed2000

Using data to improve medical practice by measuring processes and outcomes of care.

BACKGROUND: The purpose of this article is to help clinicians expand their use of data to improve medical practice performance and to do improvement research. Clinical practices can be viewed as small, complex organizations (microsystems) that produce services for specific patient populations. These services can be greatly improved by embedding measurement into the flow of daily work in the practice. WHY DO IT?: Four good reasons to build measures into daily medical practice are to (1) diagnose strengths and weaknesses in practice performance; (2) improve and innovate in providing care and services using improvement research; (3) manage patients and the practice; and (4) evaluate changes in results over time. It is helpful to have a "physiological" model of a medical practice to analyze the practice, to manage it, and to improve it. One model views clinical practices as microsystems that are designed to generate desired health outcomes for specific subsets of patients and to use resources efficiently. This article provides case study examples to show what an office-based practice might look like if it were using front-line measurement to improve care and services most of the time and to conduct clinical improvement research some of the time. WHAT ARE THE PRINCIPLES FOR USING DATA TO IMPROVE PROCESSES AND OUTCOMES OF CARE?: Principles reflected in the case study examples--such as "Keep Measurement Simple. Think Big and Start Small" and "More Data Is Not Necessarily Better Data. Seek Usefulness, Not Perfection, in Your Measures"--may help guide the development of data to study and improve practice. HOW CAN A PRACTICE START TO USE DATA TO IMPROVE CARE AND CONDUCT IMPROVEMENT RESEARCH?: Practical challenges are involved in starting to use data for enhancing care and improvement research. To increase the odds for success, it would be wise to use a change management strategy to launch the startup plan. Other recommendations include "Establish a Sense of Urgency. (Survival Is Not Mandatory)" and "Create the Guiding Coalition. (A Small, Devoted Group of People Can Change the World)." SUMMARY: Over the long term, we must transform thousands of local practice cultures so that useful data are used every day in countless ways to assist clinicians, support staff, patients, families, and communities.

Clinical Medicine↗
PubMed2000

Social phobia in a population-based female adolescent twin sample: co-morbidity and associated suicide-related symptoms.

BACKGROUND: This report attempted to replicate and extend prior work examining social phobia (SP), co-morbid psychiatric illnesses, and the risk of suicidal ideation and suicide attempts incurred by their adolescent sufferers. METHODS: SP, alcohol dependence (ALD) and major depressive disorder (MDD) diagnoses, and suicide-related symptoms, were assessed in a population-based adolescent female twin sample. The differentiation of risks as a function of co-morbidity was explored. A trivariate model was fitted to estimate sharing of genetic and environmental vulnerability between SP and co-morbid disorders. RESULTS: The lifetime prevalence of SP was 16.3 %. Significant risk for co-morbid MDD (OR = 3.2) and ALD (OR = 2.1) was observed. Strong evidence for shared genetic vulnerability between SP and MDD (respective heritabilities 28%, 45%; genetic r = 1.0) was observed with moderate support noted for similar sharing between SP and ALD (genetic r = 0.52, heritability for ALD 63%). SP with co-morbid MDD was associated with elevated risk for ALD and for suicide-related symptoms. CONCLUSIONS: SP is a common illness often followed by co-morbid MDD and ALD. SP with comorbid MDD predicts a substantially elevated risk of ALD and suicide-related symptoms, stressing the need for early SP detection.

Adolescent↗
PubMed2000

Designing an ambulatory clinical practice for outcomes improvement: from vision to reality--the Spine Center at Dartmouth-Hitchcock, year one.

Development of a new program for diagnosis and treatment of spine-related problems provided a unique opportunity to design and implement a new model for delivery of health care incorporating outcomes measurement and improvement. Key features include: application of microsystem thinking and interdisciplinary practice; integration of a uniform outcomes measurement tool, the Dartmouth Clinical Value Compass; and touch pad technology for data collection. This, for the first time, provided clinically meaningful point-of-service data and aggregated information for improvement. A further advantage was the ability to integrate a clinical research program within this microsystem. A multisite clinical research trial, the Spine Patient Outcomes Research Trial (SPORT), modeled on the Spine Center microsystem and funded by The National Institute of Arthritis, Musculoskeletal and Skin Diseases and the Office of Research on Woman's Health, the National Institutes of Health, and the National Institute of Occupational Safety and Health, the Centers for Disease Control and Prevention, is currently underway. The significant problems we face today cannot be solved by the same level of thinking that created them.

Ambulatory Care↗
PubMed2000

Routine, single-item screening to identify abusive relationships in women.

BACKGROUND: Abusive relationships are associated with several demographic factors and many clinical problems in women. However, practices often do not screen for abuse. METHODS: This is a descriptive study of 1526 women aged 19 to 69 years who completed a health survey in 31 office practices. The 53-item survey included a question designed to screen for an abusive relationship. Our analysis compared self-reported measures of symptoms (N = 13) and functional limitations (n = 6) of women who had abusive relationships with those who did not. We also examined the utility of using a constellation of clinical problems to identify risk for abuse. RESULTS: Women in abusive relationships were more likely to be poor (37% vs 14%; P < .001) and young (87% were younger than 51 years versus 69% of those who were not in such relationships; P < .001). They had twice as many bothersome symptoms (3.1 vs 1.7; P < .001) and functional problems (1.6 vs 0.8; P < .001). Approximately 40% (36/89) of low-income women with emotional problems were at risk for abuse versus only 6% (64/1025) of women with adequate financial resources and no emotional problems. However, because so many women were at low risk, almost twice as many in this group (n = 64) reported abusive relationships than in the high-risk group (n = 36). CONCLUSIONS: Women in abusive relationships have many symptoms and functional limitations. However, symptoms and clinical problems provide insufficient clues for abuse. It is better just to ask. A single-item screening question appears adequate for this purpose.

Adult↗
PubMed2000

Patrick Browne (ca. 1720-1790), Irish physician, historian and Caribbean botanist: a brief biography with an account of his lost medical dissertations.

Patrick Browne (ca. 1720-1790), a native of County Mayo, Ireland, studied medicine in Paris, graduated from the University of Rheims in 1742, and briefly continued his studies at Leiden before practising as a doctor at St Thomas's Hospital, London. Subsequently, he lived for many years in the Caribbean, in Antigua, Jamaica, Saint Croix and Montserrat, but retired to County Mayo in 1771. Browne published The civil and natural history of Jamaica in 1756 a most significant work in terms of botanical nomenclature, which included new names for 104 genera, and he promised also a volume of medical essays, but this was never printed. Fragments of his essays on venereal disease and yaws have been traced among his correspondence with Carl Linnaeus.

Academic Dissertations as Topic↗
PubMed1999

Synthesis, structure-activity relationships, and RARgamma-ligand interactions of nitrogen heteroarotinoids.

Three heteroarotinoids containing a nitrogen atom in the first ring and a C-O linking group between the two aryl rings were synthesized and evaluated for RAR and RXR retinoid receptor transactivation, tumor cell growth inhibition, and transglutaminase (TGase) induction. Ethyl 4-(N,4,4-trimethyl-1,2,3,4-tetrahydroquinolinyl)benzoate (1) contained an N-CH(3) group and activated all retinoid receptors except for RARgamma. Inceasing the hydrophobicity around the rings with analogues ethyl 4-(N,4,4,7-tetramethyl-1,2,3, 4-tetrahydroquinolin-6-oyloxy)benzoate (2) [7-methyl group added] and ethyl 4-(4,4-dimethyl-N-isopropyl-1,2,3, 4-tetrahydroquinolin-6-oyloxy)benzoate (3) [NCH(CH(3))(2) group at C-4] increased the potency and specificity for RARalpha, RARbeta, and RXRalpha, compared to 1, but had little effect on RXRbeta and RXRgamma activation. Although 1 and 3 were unable to activate RARgamma, 2 did activate this receptor with efficacy and high potency equal to that of 9-cis-retinoic acid (9-c-RA). All three heteroarotinoids exhibited 5-8-fold greater specificities for RARbeta over RARalpha. In addition, esters 1-3 inhibited the growth of two cell lines each derived from cervix, vulvar, ovarian, and head/neck tumors with similar efficiencies to that of 9-c-RA through a mechanism independent of apoptosis. The vulvar cell lines were the most sensitive, and the ovarian lines were the least sensitive. Ester 2 was similar to 1 and 3 except that 2 was a much more potent growth inhibitor of the two vulvar cell lines, which is consistent with strong RARgamma activation by 2 (but not by 1 and 3) and the high levels of RARgamma expression in skin. All three heteroarotinoids induced production of TGase, a marker of retinoid activity in human erythroleukemic cells. Esters 2 and 3 were the more potent TGase activators than 1, in agreement with the stronger activation of the RAR receptors by 2 and 3. The biological activities of these agents, and the RARgamma potency of 2 in particular, demonstrate the promise of these compounds as pharmaceutics for cancer and skin disorders.

Antineoplastic Agents↗