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Biomedical subjects

M McManus

Publications and source records attributed to M McManus.

At least 19 recordsLinked to original sources

Whither nursing? Discourses underlying the attribution of master's level performance in nursing.

AIM: Drawing upon the selected findings from a multidisciplinary study that sought to explore the meaning of master's level performance in health professional practice, the characteristics which nurse educators attributed to the practice of master's level nursing graduates are analysed to reveal underlying discourses. BACKGROUND: Although master's level programmes for nurses have been available in the United Kingdom (UK) for the past three decades and current heath policy directives link master's level qualifications with senior clinical nursing roles, the contribution that master's level education might make to the future direction of nursing is unclear. RESEARCH DESIGN AND METHODS: In-depth interviews were undertaken with a purposive sample of 18 nurse lecturers drawn from eight universities in the UK who were responsible for master's level programmes in nursing. The interview agenda explored participants' perspectives of the characteristics of master's level performance. Drawing upon the methodology of discourse analysis, interview transcripts were interpreted in such a way as to show the implicit discourses underlying the participants' claims regarding their graduate's attributes of professional practice. FINDINGS: The characteristics attributed to master's graduates were categorized under (a) cognitive competencies, (b) practice-related competencies, (c) research orientation and (d) personal dynamism. However, these attributions are not empirical generalizations, developed inductively. Rather, they draw on socially available discourses regarding the future direction of the profession. CONCLUSION: The nurse educators drew on the following socially available discourses: (a) a discourse in which nursing is construed as involving great competence in practice, but without radicality of thought. Associated with this is a pervasive rhetoric of pragmatism; (b) a discourse of interprofessional practice in which nursing has a role of leadership. This is associated with a view of the location and power of nursing within the structure of the National Health Service and (c) notably lacking were discourses of care-giving, and of academic/intellectual aspiration. The implications of these discourses for the future direction of nursing are considered.

Attitude of Health Personnel↗

Dysphagia in psychiatric patients.

1. Psychiatric patients in acute and long-term care settings may be at high risk for dysphagia and its sequelae. 2. The prevalence of dysphagia in the psychiatric population is higher than commonly believed. 3. Routine screening is essential for the safety and management of psychiatric patients at risk for dysphagia.

Adult↗

Onycholysis as a complication of systemic chemotherapy: report of five cases associated with prolonged weekly paclitaxel therapy and review of the literature.

BACKGROUND: Onycholysis has been reported in association with the use of several noncytotoxic drugs and with chemotherapy in 135 patients. Onycholysis may be precipitated by exposure to ultraviolet radiation. METHODS: The authors studied 91 patients who received paclitaxel and 187 patients who received doxorubicin. RESULTS: Onycholysis occurred in 5 of 21 patients who received > 6 courses of weekly paclitaxel, developing in the summer months in all 5 patients. It did not occur in patients who received fewer weekly paclitaxel courses or those who were treated every 3 weeks. Onycholysis did not occur in 187 patients who received doxorubicin. Review of the literature revealed that onycholysis is nearly exclusively associated with anthracycline and taxane therapy. CONCLUSIONS: Prolonged weekly paclitaxel, other taxanes, and anthracyclines cause onycholysis in some patients, which may be precipitated by exposure to sunlight. Patients receiving these drugs should protect their nails from sunlight.

Adult↗

Early therapy of vertical human immunodeficiency virus type 1 (HIV-1) infection: control of viral replication and absence of persistent HIV-1-specific immune responses.

Studies of potent antiretroviral combination regimens were undertaken in young infants to evaluate the potential for long-term suppression of viral replication and to evaluate the immune consequences of such therapies. Early combination antiretroviral therapy led to a loss of plasma viremia, cultivable virus, and labile extrachromosomal replication intermediates. Despite preservation of immune function, persistent human immunodeficiency type 1 (HIV-1)-specific immune responses were not detected in most infants. The absence of detectable, persisting immune responses in most HIV-1-infected infants treated early contrasts with what is typically seen in adults who are treated early. These results are consistent with the notion that early combination antiretroviral therapy of HIV-1-infected infants allows the long-term suppression of viral replication.

Anti-HIV Agents↗

Access to health care for children with special health care needs.

OBJECTIVE: To assess the role health insurance plays in influencing access to care and use of services by children with special health care needs. METHODS: We analyzed data on 57 553 children younger than 18 years old included in the 1994-1995 National Health Interview Survey on Disability. The survey obtained information on special health care needs, insurance status, and access to and use of health services. Bivariate and multivariate analyses were used to assess the association of insurance with several measures of access and utilization, including usual source of care, site of usual care, missed or delayed care, and use of ambulatory physician services. RESULTS: Using the federal Maternal and Child Health Bureau definition of children with special health care needs, we estimate that 18% of US children under 18 years old had an existing special health care need in 1994-1995. An estimated 89% of these children had some form of health insurance coverage, most often private health insurance. Insured children were more likely than uninsured children to have a usual source of care (96.9% vs 79.2%). Among those with a usual source of care, insured children were more likely than uninsured children to have an identified regular clinician (87. 6% vs 80.7%). Insured children were less likely to report unmet health needs, including medical care (2.2% vs 10.5%), dental care (6. 1% vs 23.9%), prescriptions, and/or eyeglasses (3.1% vs 12.3%), and mental health care (.9% vs 3.4%). Insured children were also more likely to have a physician contact in the past year (89.3% vs 73.6%) and have more physician contacts on an annual basis (8.5 vs 4.1 contacts). Unexpectedly, no differences were found between insured and uninsured children in availability of after hours medical care (evenings and weekends) or satisfaction with care. We also found some modest differences in access between publicly and privately insured children. Privately insured children were more likely to have a usual source of care (97.6% vs 95.3%) and a regular clinician (91.0% vs 81.1%). Privately insured children were also less likely to report dissatisfaction with care at their usual site of care (14. 9% vs 21.0%) and have access to care on evenings and weekends (6.8% vs 13.4%). No substantial differences were found between privately and publicly insured children in prevalence of unmet health needs or delays in obtaining care due to cost. CONCLUSIONS: This study illustrates the importance of health insurance for children with special health care needs. Continued efforts are needed to ensure that all children with special health care needs have insurance and that remaining access and utilization barriers for currently insured children with special health care needs are also addressed.

Adolescent↗

Some dilemmas of master's level nurse education.

Despite an increase in the growth of master's level provision for qualified nurses in the United Kingdom uncertainty exists regarding the characteristics of master's level performance in respect of professional practice. This paper presents selected findings from a multidisciplinary study that sought to examine the characteristics of master's level performance in health professional courses that had an expressed practice orientation. It focuses specifically on dilemmas nurse educators encountered in relation to British master's level nurse education. Following an initial pilot stage involving focus group interviews with separate groups of nurses, occupational therapists and physiotherapists, an interview agenda was developed to explore participants' perspectives of the characteristics of master's level performance. Individual in-depth interviews were undertaken with a purposive sample of 18 nurse educators drawn from eight universities in England. Interview transcripts were coded and thematically analysed. Six kinds of dilemma emerged from the interviews. These were breadth vs. depth in the conceptualization of master's level for nursing, relevance to practice vs. academic detachment, facilitating creative thinking vs. reinforcing rigidity, encouraging or suppressing different modes of critical thinking, postgraduate nurses as loyal change agents vs. the problem of well-qualified mavericks, and professional experience as facilitating or hindering master's level performance. These dilemmas raise important questions about course design and the role of stakeholders in determining curriculum content. Moreover, a pervasive tension between a utilitarian emphasis on the application and utility of knowledge on one hand, and aspirations to promote creativity and critical thinking which look to alternative possibilities on the other hand, suggests that nurse educators exercise a degree of conservatism in relation to master's level. It is concluded that this apparent quest to maintain a safe variant of the status quo as the best way of promoting the wellbeing of patients should be subject to profound questioning.

Attitude of Health Personnel↗

Molecular cloning, expression, localisation and functional characterisation of a rabbit SULT1C2 sulfotransferase.

The importance of sulfotransferases in xenobiotic metabolism is gaining recognition. The gastrointestinal (GI) tract is a major portal of entry for many xenobiotics, yet little is known about the contribution of sulfotransferases to detoxication or bioactivation metabolism in these tissues. To this end, isolation and characterisation of sulfotransferases expressed in the stomach of rabbits was undertaken. A unique sulfotransferase cDNA (GenBank Accession No. AF026304) was isolated from a rabbit stomach cDNA library. This cDNA was 1439 base pairs (bp) long and has an open reading frame of 888 bp. On expression of the cDNA in both COS cells and E. coli, a protein molecular weight of 34 kDa was detected on SDS-PAGE. Immunoblotting using an antibody raised in goats against the bacterially expressed protein detected expression of the protein in GI tract tissues. The 34 kDa immunoreactive band was detected in rabbit GI tract tissues (stomach, duodenum, jejunum, ileum, colon, caecum and rectum), liver and kidneys, but not in the lungs (n = 3). The human ortholog (GenBank Accession No AF026303) of the rabbit enzyme was cloned from a human stomach cDNA library. These two enzymes share 84% amino acid sequence identity and have been termed 1C2 sulfotransferases. When functional and kinetic characterisation of the recombinant rabbit and human proteins was carried out using 16 known ST substrates, detectable sulfonation activity was observed only with p-nitrophenol (with Km values of 2.2 mM and 13.3 mM, respectively). In conclusion, we have identified a rabbit GI tract sulfotransferase belonging to a newly defined sulfotransferase subfamily.

Amino Acid Sequence↗

'Levels' of attainment in nursing practice: reality or illusion?

In earlier research based on an analysis of course documentation, it had been found that there was little consensus among nurse educators concerning the parameters which distinguish levels of practice skills, particularly those which differentiate diploma and degree qualifications in the United Kingdom. This result was confirmed and strengthened in the current study. Lecturers in nursing, when presented with a sorting task using 40 statements derived from course documentation selected from the earlier study, were unable to distinguish statements describing diploma level from those describing degree level practice. Possible reasons for the difficulty are discussed. It is concluded that the attempt to represent practice skill in a hierarchy of assessment for degree or diploma qualifications is premature since the parameters of practice remain unreliably specified.

Achievement↗

Dynamics of human immunodeficiency virus type 1 replication in vertically infected infants.

Plasma human immunodeficiency virus type 1 (HIV-1) turnover and kinetics were studied in children aged 15 days to 2 years following the initiation of a triple antiretroviral drug regimen consisting of zidovudine, lamivudine, and nevirapine. HIV-1 turnover was at least as rapid as that previously described in adults; turnover rates were more rapid in infants and children aged 3 months to 2 years than in infants less than 3 months of age. These data confirm the central role of HIV-1 replication in the pathogenesis of vertical HIV-1 infection and reinforce the importance of early, potent combination therapies for the long-term control of HIV-1 replication.

Acquired Immunodeficiency Syndrome↗

Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery.

OBJECTIVE: Stereotactic radiosurgery is increasingly being used to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. The purpose of this study was to retrospectively evaluate the effectiveness of radiosurgery in the treatment of hemangioblastomas. METHODS: From 1989 to 1996, 29 hemangioblastomas in 13 patients with von Hippel-Lindau disease were treated with linear accelerator-based radiosurgery. The mean patient age was 40 years (range, 31-57 yr). The radiation dose to the tumor periphery averaged 23.2 Gy (range, 18-40 Gy). The mean tumor volume was 1.6 cm3 (range, 0.07-65.4 cm3). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic and magnetic resonance imaging scans. The mean follow-up period was 43 months (range, 11-84 mo). RESULTS: Only one (3%) of the treated hemangioblastomas progressed. Five tumors (17%) disappeared, 16 (55%) regressed, and 7 (24%) remained unchanged in size. Five of nine patients with symptoms referable to treated hemangioblastomas experienced symptomatic improvement. During the follow-up period, one patient died as a result of progression of untreated hemangioblastomas in the cervical spine. Three patients developed radiation necrosis, two of whom were symptomatic. CONCLUSION: Although follow-up monitoring is limited, stereotactic radiosurgery provides a high likelihood of local control of hemangioblastomas and is an attractive alternative to multiple surgical procedures for patients with von Hippel-Lindau disease.

Adult↗

An epidemiologic profile of children with special health care needs.

OBJECTIVE: To present an epidemiologic profile of children with special health care needs using a new definition of the population developed by the federal Maternal and Child Health Bureau. METHODS: We operationalized the new definition using the recently released 1994 National Health Interview Survey on Disability. Estimates are based on 30 032 completed interviews for children <18 years old. The overall response rate was 87%. RESULTS: Eighteen percent of US children <18 years old in 1994, or 12.6 million children nationally, had a chronic physical, developmental, behavioral, or emotional condition and required health and related services of a type or amount beyond that required by children generally. This estimate includes children with existing special health care needs but excludes the at-risk population. Prevalence was higher for older children, boys, African-Americans, and children from low-income and single-parent households. Children with existing special health care needs had three times as many bed days and school absence days as other children. An estimated 11% of children with existing special health care needs were uninsured, 6% were without a usual source of health care, 18% were reported as dissatisfied with one or more aspects of care received at their usual source of care, and 13% had one or more unmet health needs in the past year. CONCLUSIONS: A substantial minority of US children were identified as having an existing special health care need using national survey data. Children with existing special health care needs are disproportionately poor and socially disadvantaged. Moreover, many of these children face significant barriers to health care.

Adolescent↗

Casting the net for "depression" among ethnic minority children from the high-risk urban communities.

This paper reviews the current research on depressive phenomena among urban ethnic minority children from resource-poor communities. Developmental differences in the prevalence and reporting of depressive phenomena are discussed. The relationships between depressive phenomena and stressful life events, parental styles, anxiety, child-coping strategies, and scholastic maladjustment are explored. The authors critique the psychometric equivalency, construct validity, diagnostic sensitivity, and terminology of the Children's Depression Inventory (CDI). Methodological and conceptual alternatives are proposed, and the utility and validity of various measures of depressive phenomena in children are examined. The review highlights the authors's perspective that a depressive phenomenon among young school-aged children from resource-poor communities is best described as a complex response to environment, rather than a biologically determined disease entity.

Adolescent↗

Strengthening partnerships between state programs for children with special health care needs and managed care organizations.

The roles and responsibilities of state Title V Programs for Children with Special Health Care Needs (CSHCN) are changing with the rapid expansion of managed care. The authors surveyed Title V CSHCN programs to learn about critical issues and examples of collaboration with managed care organizations in the following areas: (1) defining and identifying children with special health care needs, (2) enrollment assistance and family participation, (3) pediatric provider and service requirements, (4) education and training, (5) quality of care, and (6) pediatric risk-adjusted capitation mechanisms. This article also includes recommendations developed by the federal Maternal and Child Health Bureau's Work Group on Managed Care.

Capitation Fee↗

Intracellular electrolytes regulate the volume set point of the organic osmolyte/anion channel VSOAC.

Regulation of the volume sensitivity of the swelling-activated organic osmolyte/anion channel VSOAC by intracellular electrolytes was examined in intact and patch-clamped C6 glioma cells. In intact cells, VSOAC activation was monitored by [3H]taurine efflux measurements, and intracellular electrolyte concentrations were manipulated by acclimation to hypertonic medium for varying periods of time. Hypertonic shrinkage was followed by a rapid and complete regulatory volume increase mediated by electrolyte accumulation that elevated intracellular Na+, K+, and Cl- concentrations. During prolonged (4-48 h) exposure to hypertonicity, electrolyte concentrations decreased gradually as cells accumulated the organic osmolyte myo-inositol. VSOAC activation induced by cell swelling of 35-40% increased as a function of the time of exposure to hypertonicity and was inversely correlated with measured intracellular Na+, K+ and Cl- levels. In patch-clamped cells, swelling-induced Cl- current activation was unaffected by acclimation conditions but was inhibited by increasing the concentration of electrolytes in the patch pipette solution. Quantification of the relationship between VSOAC activation and cell swelling demonstrated that increases in intracellular electrolyte levels increase VSOAC volume set point. Regulation of VSOAC volume sensitivity by electrolytes allows cells to selectively utilize electrolytes or a combination of electrolytes and organic osmolytes for regulatory volume decrease (RVD). Control over the type of solute used for volume regulation is advantageous, allowing cells to control intracellular ionic composition and prevent increases in cytoplasmic ionic strength during RVD.

Animals↗

Insertional and deletional RNA editing in trypanosome mitochondria.

The mitochondrial mRNAs of trypanosomes are often post-transcriptionally modified by an RNA processing event, termed RNA editing, which results in the insertion or deletion of uridylate (U) residues in mRNAs. RNA editing is necessary for the formation of complete coding sequences for several essential mitochondrial proteins. The number and site of U addition and deletion is directed by small guide RNAs (gRNAs). Recent studies indicate that the mechanism of RNA editing in trypanosomes involves a series of enzymatic steps. We show that the initial step in this enzymatic cascade requires the formation of a binary RNA complex between the gRNA and its cognate pre-mRNA. Depletion of specific gRNAs inhibits cleavage of the pre-mRNA by an editing site specific endoribonuclease. Addition of synthetic gRNAs reverses this inhibition. All of the activities needed for RNA editing in vitro are present within a 19S ribonucleo-protein complex (RNP) composed of gRNAs, the editing site specific endonuclease, an RNA ligase, a terminal uridylate transferase (TUTase) and approximately 15 other unidentified proteins. We have recently identified and cloned the gene for a 45kDa protein, the RNA Editing Associated Protein-1 (REAP-1), which is a component of trypanosome editing complexes. REAP-1 co-purifies with RNA ligase and TUTase activities and is part of a > 700 kDa RNP containing gRNAs. Antibodies against REAP-1 inhibit in vitro RNA editing reactions confirming its role in RNA editing.

Animals↗

Assessment of the DNA adduction and pharmacokinetics of PhIP and MeIOx in rodents at doses approximating human exposure using the technique of accelerator mass spectrometry (AMS) and 32P-postlabeling.

Estimating the cancer risk posed by heterocyclic amines depends on measuring how chemical dose influences measurable indicators of cancer progression. This data ideally should encompass the range of actual human exposure, at the low dose end, and laboratory animal studies, at the high dose end. Accelerator mass spectrometry (AMS) has been used to measure the absorption, fate, and DNA adduct dosimetry of the heterocyclic amines PhIP and MeIQx at doses equivalent to human consumption following single-dose administration and chronic daily dosing. AMS is a nuclear physics technique which specifically counts nuclei of cosmogenic isotopes, rather than relying on decay. For tracing 14C, sensitivity is increased 10(6)-fold relative to decay counting. We have found that tissue clearance rates for [2-(14)C]-PhIP are rapid (t1/2 = 1 h) at low dose (41 ng/kg), with most of the radiocarbon distributed to the liver and G.I. tract. MeIQx-DNA adduct levels decrease linearly with dose (5 mg/kg-500 ng/kg) in single dose exposures. Likewise, the biologically available dose of [2-(14)C]-MeIQx decreases linearly with decreasing dose (5 mg/kg-1 ng/kg). On chronic daily dosing, it takes 40 days for adducts to reach steady-state in tissues and adduct levels appear to decrease linearly with decreasing dose, except possibly at very low doses. DNA binding of PhIP involves both sulfation or acetylation of the N-hydroxylated PhIP. Quantitatively, sulfation appears to be an important pathway for PhIp activation in rodent tissue cytosols while acetylation appears quantitatively more important in human tissue cytosols. The greatest activity is in liver and intestinal tissues for both pathways. The specific DNA adducts formed in vivo and in vitro from exposure to PhIP and MeIQx are likely guanine adducts. These data suggest that DNA adduct dosimetry responds linearly with dose but may become sub-linear at very low doses for chronic exposure and that factors other than DNA adduction may be critical to explain these heterocyclic amines' tumorigenicity.

Animals↗

Ketoconazole blocks organic osmolyte efflux independently of its effect on arachidonic acid conversion.

Ketoconazole, cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate, and gossypol are reported inhibitors of the lipoxygenase (LO) and cytochrome P-450 enzyme systems and are potent blockers of swelling-activated efflux of organic osmolytes and volume-sensitive anion channels in C6 glioma cells. To directly test the hypothesis that LO- or cytochrome P-450-derived products of arachidonic acid (AA) participate in the regulation of these volume-sensitive transport pathways, we incubated C6 cells with [1-14C]AA and observed the extent and profile of its conversion under basal conditions and after acute swelling. High-performance liquid chromatographic analysis revealed that most (70-80%) of the labeled AA remained unchanged with only 6-8% and 10-20% of label converted to LO- [12(S)- and 15(S)-hydroxyeicosatetraenoic acid (12- and 15-HETE)] and cyclooxygenase- [prostaglandin (PG) E2 and PGF2a] derived products, respectively. Leukotrienes and epoxyeicosatrienoic acid compounds were not produced. The conversion profile of [1-14C]AA was not altered substantially by cell swelling. Treatment of cells with the LO-derived products 5-, 12-, and 15-HETE or their immediate metabolic precursors, 5(S)-, 12(S)-, and 15(S)-hydroxyperoxyeicosatetraenoic acid, at 5 microM concentrations did not stimulate efflux of [3H]inositol. In addition, treatment with HETEs did not override the inhibition of efflux observed with the LO-cytochrome P-450 blocker ketoconazole. Whole cell patch-clamp experiments demonstrated that volume-sensitive anion channels, the postulated pathway for organic osmolyte efflux in C6 cells, are rapidly and reversibly blocked by ketoconazole in a fashion suggestive of direct inhibition rather than via interruption of a second messenger pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗