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Biomedical subjects

E Walker

Publications and source records attributed to E Walker.

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

Medical symptoms without identified pathology: relationship to psychiatric disorders, childhood and adult trauma, and personality traits.

Community studies have shown that stressful life events, psychological distress, and depressive and anxiety disorders are associated with 1) a range of medical symptoms without identified pathology, 2) increased health care utilization, and 3) increased costs. In both primary care and medical specialty samples, patients who have syndromes with ill-defined pathologic mechanisms (such as the irritable bowel syndrome and fibromyalgia) have been shown to have significantly higher rates of anxiety and depressive disorders than do patients with comparable, well-defined medical diseases and similar symptoms. Other studies show that after adjustment for severity of medical illness, patients with depression or anxiety and comorbid medical disease have significantly more medical symptoms without identified pathology than do patients with a similar medical disease alone. Both childhood maltreatment and psychological trauma in adulthood have been associated with increased vulnerability to psychiatric illness and more medical symptoms. The substantial functional impairment, distress, and costs associated with medical symptoms without identified pathology suggest that research studies promoting a better understanding of the biopsychosocial cause of these symptoms may yield pragmatic, cost-effective approaches to treatment in medical settings.

Adult↗
PubMed2001

Synergistic growth inhibition of prostate cancer cells by 1 alpha,25 Dihydroxyvitamin D(3) and its 19-nor-hexafluoride analogs in combination with either sodium butyrate or trichostatin A.

Prostate cancer is a major cause of male cancer death. In vitro and in vivo data support a role for 1 alpha,25 Dihydroxyvitamin D(3) (1 alpha,25(OH)(2)D(3)) in regulating the growth and differentiation of the normal prostate gland yet prostate cancer cells appear significantly less sensitive to this action. Vitamin D(3) receptor (VDR) content or mutational status do not correlate clearly with the antiproliferative effects of 1 alpha,25(OH)(2)D(3) and therefore it is unclear why prostate cancer cell lines are significantly less sensitive to this action. We hypothesized that the antiproliferative responses of prostate cancer cells to 1 alpha,25(OH)(2)D(3) are suppressed by a process involving histone deacetylation. Sodium butyrate (NaB) and trichostatin A (TSA) are inhibitors of histone deacetylase (HDAC) activity. Low doses of NaB or TSA (300 microM and 15 nM respectively), which alone were relatively inactive, synergized with 1 alpha,25(OH)(2)D(3) in liquid and semi-solid agar to inhibit the growth of LNCaP, PC-3 and DU-145 prostate cancer cells. Still greater synergy was observed between vitamin D(3) hexafluoride analogs and either NaB or TSA. The mechanism appeared to involve neither the cyclin-dependent kinase inhibitor, p21((waf1/cip1)) nor cell cycle arrest, but rather induction of apoptosis. These data suggest that cells dysregulate the normal pro-apoptotic signals of 1 alpha,25(OH)(2)D(3) during prostate cancer development by a mechanism involving histone deacetylation. Combination therapy with potent vitamin D(3) analogs and clinically approved HDAC inhibitors may overcome this lesion and improve the treatment of both androgen-dependent and independent prostate cancer.

Antineoplastic Agents↗
PubMed2001

A randomized trial of relapse prevention of depression in primary care.

BACKGROUND: Despite high rates of relapse and recurrence, few primary care patients with recurrent or chronic depression are receiving continuation and maintenance-phase treatment. We hypothesized that a relapse prevention intervention would improve adherence to antidepressant medication and improve depression outcomes in high-risk patients compared with usual primary care. METHODS: Three hundred eighty-six patients with recurrent major depression or dysthymia who had largely recovered after 8 weeks of antidepressant treatment by their primary care physicians were randomized to a relapse prevention program (n = 194) or usual primary care (n = 192). Patients in the intervention group received 2 primary care visits with a depression specialist and 3 telephone visits over a 1-year period aimed at enhancing adherence to antidepressant medication, recognition of prodromal symptoms, monitoring of symptoms, and development of a written relapse prevention plan. Follow-up assessments were completed at 3, 6, 9, and 12 months by a telephone survey team blinded to randomization status. RESULTS: Those in the intervention group had significantly greater adherence to adequate dosage of antidepressant medication for 90 days or more within the first and second 6-month periods and were significantly more likely to refill medication prescriptions during the 12-month follow-up compared with usual care controls. Intervention patients had significantly fewer depressive symptoms, but not fewer episodes of relapse/recurrence over the 12-month follow-up period. CONCLUSIONS: A relapse prevention program targeted to primary care patients with a high risk of relapse/recurrence who had largely recovered after antidepressant treatment significantly improved antidepressant adherence and depressive symptom outcomes.

Adolescent↗
PubMed2001

How do we facilitate carers' involvement in decision making?

BACKGROUND: Government health care policy urges service providers to involve service users in the decision-making process. Research studies have recommended changes to current health care practice to facilitate this involvement. However, carers' organizations continue to highlight a gap between policy and practice in relation to involvement. AIM: The aim of the study reported on in this paper was to investigate involvement in a specific health care context with a view to identifying both opportunities for change and practical, realistic ways of bringing about that change. This was a qualitative case study using a case study design. The field site selected was a respite and assessment (23 bedded) ward within the Psychiatric Unit of a hospital specializing in the care of older people. Informal carers (n=20) and members of the multidisciplinary team (n=29) were interviewed about their views and experiences. The interviews were audiorecorded and transcribed. Family meetings, multidisciplinary team meetings and ward routines were the focus of non-participant observation. Field notes from these observations, together with the interview data were analysed using constant comparative method. RESULTS AND CONCLUSIONS: The reported experiences of carers in this study highlighted four markers of satisfactory involvement: feeling that information is shared; feeling included in decision making; feeling that there is someone you can contact when you need to; and feeling that the service is responsive to your needs. The majority of carers felt dissatisfied with the level of involvement. The situation we found echoed that found in other studies, i.e. the majority of informal carers (henceforth 'carers') interviewed were dissatisfied with the level of their involvement. However, our investigation, in which the views of health care professionals as well as those of carers were sought, provided invaluable insight into why this might be the case. Two main sources of difficulty were found: hospital systems and processes, and the relationship between nursing staff and carers. The argument made is that practitioners themselves must notice and challenge these barriers if carer involvement is to be facilitated.

Aged↗
PubMed2001

Differences in repair responses between immature and mature cartilage.

Cartilage has a poor reparative capacity although it is unclear as to what extent this may be dependent on age or maturation. In the current study, the cellular responses of chondrocytes to experimental wounding in vitro using embryonic, immature, and mature cartilage have been compared. In all cases, the response was consistent (a combination of cell death that included apoptosis and proliferation). The speed of response varied in terms of cell death with embryonic cartilage showing the most rapid response and mature cartilage showing the slowest response. Intrinsic repair as assessed by the ability to heal the lesion was not detected in any of the culture systems used. It was concluded that the poor repair potential of cartilage is not maturation dependent in the systems studied.

Animals↗
PubMed2001

Dopamine receptors in the brains of schizophrenia patients: a meta-analysis of the findings.

Controversy surrounds the question of whether there are dopamine (DA) receptor abnormalities in the brains of schizophrenia patients; in particular, whether DA receptors of the D2 family are elevated in density. Methodological factors and sample characteristics have been postulated to account for differences in study outcome, but there has been no systematic analysis of the contribution of these factors to study effect sizes. This meta-analysis of the research findings sought to determine the influence of methodologic factors and sample characteristics on the magnitude of diagnostic group differences in DA D2 density (Bmax) and affinity (Kd). The analysis suggests at least moderate effects, such that schizophrenia patients show an elevation in both values when compared to controls. These effects are amplified in medicated patients, but not solely attributable to antipsychotics. The group differences in DA D2 receptor density and affinity increase with age among nonmedicated patients. The use of a butyrophenone ligand also yields larger effects. It is concluded that a subgroup of schizophrenia patients manifests increased DA D2 receptor density and decreased receptor affinity. In the absence of medication, these changes may become more pronounced with age. Differences in study outcome are also partially due to methodologic factors, including the ligand.

Antipsychotic Agents↗
PubMed2001

Mental illness, functional impairment, and patient preferences for collaborative care in an uninsured, primary care population.

OBJECTIVE: Our goal was to compare the prevalence of mental illness and its impact on functional status in an indigent uninsured primary care population with a general primary care sample. We also hoped to assess patient preferences about mental health and medical service integration. STUDY DESIGN: We compared a survey of consecutive primary care adults in April and May 1999 with a 1997-98 survey of 3000 general population primary care patients. Both studies used the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire and the 20-question Medical Outcomes Study Short Form. POPULATION: The patients were from a private nonprofit primary care clinic in Grand Junction, Colorado, that served only low-income uninsured people. We approached a total of 589 consecutive patients and enrolled 500 of them. MAIN OUTCOME MEASURE: The main outcomes were the prevalence of psychiatric illnesses and the relationship with functional impairment. We compared our findings with a more generalizable primary care population. RESULTS: This low-income uninsured population had a higher prevalence of 1 or more psychiatric disorders (51% vs 28%): mood disorders (33% vs 16%), anxiety disorders (36% vs 11%), probable alcohol abuse (17% vs 7%), and eating disorders (10% vs 7%). Having psychiatric disorders was associated with lower functional status and more disability days compared with not having mental illness. Patients indicated a preference for mental health providers and medical providers to communicate about their care. CONCLUSIONS: This low-income uninsured primary care population has an extremely high prevalence of mental disorders with impaired function. It may be important in low-income primary care settings to include collaborative care designs to effectively treat common mental disorders, improve functional status, and enhance patient self-care.

Adolescent↗
PubMed2001

Functional classification of interferon-stimulated genes identified using microarrays.

Interferons (IFNs) are a family of multifunctional cytokines that activate transcription of subsets of genes. The gene products induced by IFNs are responsible for IFN antiviral, antiproliferative, and immunomodulatory properties. To obtain a more comprehensive list and a better understanding of the genes regulated by IFNs, we compiled data from many experiments, using two different microarray formats. The combined data sets identified >300 IFN-stimulated genes (ISGs). To provide new insight into IFN-induced cellular phenotypes, we assigned these ISGs to functional categories. The data are accessible on the World Wide Web at http://www.lerner.ccf.org/labs/williams/, including functional categories and individual genes listed in a searchable database. The entries are linked to GenBank and Unigene sequence information and other resources. The goal is to eventually compile a comprehensive list of all ISGs. Recognition of the functions of the ISGs and their specific roles in the biological effects of IFNs is leading to a greater appreciation of the many facets of these intriguing and essential cytokines. This review focuses on the functions of the ISGs identified by analyzing the microarray data and focuses particularly on new insights into the protein kinase RNA-regulated (PRKR) protein, which have been made possible with the availability of PRKR-null mice.

Animals↗
PubMed2000

Monoclonal antibodies to CD45 modify LPS-induced arachidonic acid metabolism in macrophages.

Signaling by lipopolysaccharide (LPS) through CD14 involves the activation of protein tyrosine kinases of the src family and leads to cytokine production and activation of arachidonic acid metabolism in macrophages. CD45 protein tyrosine phosphatase (PTPase) might play a role in modulating the response through this pathway. Although a critical role in regulation of T-cell signaling for CD45 has been demonstrated, little is known about its role in macrophages. Monoclonal antibodies to CD45 and F(ab')(2) fragments of the monoclonal antibody enhanced the response of differentiated THP-1 monocytic cells to LPS for the release of radiolabeled arachidonic acid metabolites, prostaglandin E(2), and tumor necrosis factor alpha. The enhancing effect of anti-CD45 mAbs was shown to occur primarily through CD14-dependent signaling by performing the experiments under conditions favoring that pathway. Further, LPS may be able to alter the enzymatic activity of CD45, as shown by Western blots of CD45 immunoprecipitates in which LPS caused a transient change in the phosphorylation state of CD45. We conclude that CD45 appears to play a role in LPS-induced responses through the CD14 pathway, possibly through its PTPase activity.

Animals↗
PubMed2000

Lymphatic filariasis in the Philippines.

Lymphatic filariasis caused by Wuchereria bancrofti and Brugia malayi is endemic throughout most of the southern half of the Philippine archipelago. Economic and manpower shortages prior to 1996 made it difficult to acquire new prevalence data and vector control data concurrently from all provinces. Nevertheless, analysis of cumulative prevalence data on filariasis indicates the persistence of filariasis in each of the three major island groups - Luzon, Visayas and Mindanao - including 45 out of 77 provinces. Here, Michael Kron and colleagues summarize the prevalence data, and review host, parasite and vector characteristics relevant to the design and implementation of disease control initiatives in the Philippines planned for the year 2000.

Animals↗
PubMed2000

Moving on from interpretivism: an argument for constructivist evaluation.

Moving on from interpretivism: an argument for constructivist evaluation This paper examines the research process in the context of an evaluation of work-based learning. The findings of the evaluation are used to illustrate issues around roles and relationships within interpretivist research where a separation is maintained between the researcher, as investigator, and the participants, as the subject of their investigation. The discussion focuses on: the threatening nature of evaluation and the way in which that affects the process of inquiry and learning; the ways in which people's perceptions of research can act as barriers to the implementation of change; and the consequences of this role separation for practice development. In exploring these issues the paper argues for an approach to evaluation research which (a) emphasizes collaboration, (b) is orientated to change and (c) treats the evaluation process as a learning opportunity through which professionals acquire the skills and knowledge to investigate and advance their own practice.

Attitude of Health Personnel↗
PubMed2000

Integrating complementary medicine into the nursing curriculum.

As nursing moves into the next century, the changing role of the nurse and increasing scope for practice will create the potential to develop an integrated approach to healthcare and the use of complementary medicine alongside more orthodox care. This paper outlines some of the forces which are creating a change in healthcare integration and discusses the value of pre-registration education and training in helping to make future nursing practitioners understand the use and benefit of complementary medicine. In promoting complementary medicine within the pre-registration curriculum, the process of reflection helped nurse teachers to appreciate the potential to integrate it into nurse training.

Complementary Therapies↗
PubMed2000

Are there detectable differences in quality of care or outcome of depression across primary care providers?

OBJECTIVE: The objective of this work was to determine whether there are detectable differences among primary care physicians in measures of quality of care or clinical outcome for depressed patients during the first 2 months of treatment with antidepressant medication. METHODS: We studied 1,599 depressed primary care patients initiating antidepressant treatment from 63 family physicians in 4 primary care clinics of a staff-model health maintenance organization. Patients were interviewed 6 to 8 weeks after initiating antidepressant medication with a telephone structured interview that included the Structural Clinical Interview for DSM-IV Diagnoses (SCID). Automated databases of the HMO were used to examine 3 quality-of-care measures: (1) the percentage of patients who had a refill of their antidepressant by 6 weeks, (2) the percentage of patients who had a return visit by 3 weeks, and (3) the percentage of patients having a return visit by 6 weeks. The percentage of patients in each primary care physician panel who had > or =4 persistent DSM-IV depressive symptoms at 6 to 8 weeks was the main clinical outcome variable. To adjust for case-mix differences between physician panels, patient age, gender, and medical comorbidity were controlled for in the analyses. Two covariates were used to adjust for differences in patients' clinical severity: self-report of > or =2 prior depressive episodes and an SCID diagnosis of major depression during the patient's worst episode in the last 2 years. Physician age, gender, and part-time versus full-time practice were also used as covariates. RESULTS: The wide observed range of variability in quality-of-care and clinical outcome measures by physician practice decreased markedly in the statistical model that controlled for patient-level covariates and differences in the number of patients seen per provider. We did not detect differences in physician practice for the percentage of patients who had a return visit by 3 or 6 weeks, the percentage of patients who had a refill of their antidepressant prescription by 6 weeks, or the percentage of patients with an adverse clinical outcome of depression. CONCLUSIONS: We did not find important differences in measures of quality of care or patient outcomes by physician. These results may have implications for the use of physician profiling and other forms of physician report cards.

Adolescent↗
PubMed2000

Domestic violence: the shaken adult syndrome.

A case of domestic violence is reported. The patient presented with the triad of injuries associated with the shaking of infants: retinal haemorrhages, subdural haematoma, and patterned bruising; this has been described as the shaken adult syndrome. This case report reflects the difficulties in diagnosing domestic violence in the accident and emergency setting.

Adult↗
PubMed2000

The design, implementation, and acceptance of a primary care-based intervention to prevent depression relapse.

OBJECTIVE: This article describes the conceptual underpinnings, implementation, and participation rates of a twelve-month low-intensity primary care-based intervention to prevent depression relapse. The intervention was designed to address the inherent problems in delivery of effective maintenance treatment in a population based sample of primary care patients. METHODS: Patients at high risk of relapse based on psychiatric history who recovered from depression six to eight weeks after initiation of pharmacotherapy by their primary care physician were eligible; 194 were randomized to receive the intervention. The intervention combined education about depression, motivation-enhancing shared decision-making regarding the use of maintenance pharmacotherapy, and cognitive-behavioral strategies. The program included two visits with a Depression Prevention Specialist working in tandem with the primary care physician at the primary care clinic, with supervision and back up from a consulting psychiatrist, proactive follow-up telephone calls and mailed personalized feedback. RESULTS: Ninety-three percent of patients attended both in-person visits; 97 percent attended one visit. Eighty percent of patients completed all three follow-up telephone calls, and 85 percent returned at least one mailed feedback form; 48 percent returned all four forms. Offered a menu of options for self-management, most patients chose medication as well as a variety of behavioral strategies. At six months, 72 percent ofpatients and at twelve months 62 percent of patients remained on antidepressant medication. CONCLUSIONS: We conclude that it is feasible to integrate a low intensity, twelve-month relapse prevention intervention for depression into a primary care clinic.

Antidepressive Agents↗
PubMed2000

Assessing the implementation of workplace health programs outside of controlled environments.

The study explored the implementation of workplace health programmes in 14 NHS Trusts (hospitals). It sought to identify different approaches to implementation and measures that could be used to guide future development. The study comprised inter-related elements examining the process of implementing workplace health and the impact on staff. An innovative action research approach was applied to the evaluation. The aims of the evaluation were to generate activity and learning within the organisations which was sustainable (long term) and transferable outside the study organisations. The study is described in terms of the multiple methods and the ways in which these have been brought together in the analysis. The approach has been informed by a shift from an individualistic perspective towards one which sees the health of workers within the broader context of organisational development and management. The research identified a number of dilemmas for workplace health with its focus on the health of the individual. A typology was developed which describes different approaches to workplace health and their impact on sustaining such initiatives. It suggests that for workplace health to be successful it must address the organisational context as well as individual staff needs. Results from a survey of staff in the 14 trusts seems to demonstrate an association between the approaches, described in the typology, and an impact on staff. Workplace health programmes need to shift towards approaches where the individual's health is seen within the wider context of the organisation.

Health Promotion↗