Nurse practitioners. Testing the boundaries.
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Humans↗
Biomedical subjects
C Jackson
Publications and source records attributed to C Jackson.
HVA. Naming the change.
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Community Health Nursing↗
The market is the message.
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Community Health Nursing↗
Epidemiologic evidence for clustering of equine motor neuron disease in the United States.
OBJECTIVE: To examine the regional variations in the distribution of equine motor neuron disease (EMND) in the United States and the factors that might explain those variations. DESIGN: Cluster investigation and case-control study. SAMPLE POPULATION: The study population consisted of 97 horses with histopathologically confirmed EMND and 698 controls with diagnosis of other spinal cord disorders at 21 US veterinary teaching hospitals participating in the Veterinary Medical Data Base. PROCEDURE: The total horse population of the United States was divided into 21 regions, and the regional incidence rates of EMND from January 1985 through January 1995 were estimated. Moran's index of spatial autocorrelation was calculated to test for spatial clustering of the disease. The 21 regions were then joined in broader areas according to the similarity of their EMND rates by means of the cluster analysis statistical technique. Finally, the role of potential confounding factors (age at diagnosis, month of diagnosis, breed, and sex) in the present distribution of EMND was assessed, using logistic regression analysis. RESULTS: Differences in estimated rates across the 21 regions resulted in a strong pattern of spatial clustering of EMND in the United States. The geographic units were grouped into 5 risk regions, with the gradient of EMND incidence rates increasing from the western states (almost 0 cases/1,000,000 horse-years) toward New England (20.78 cases/1,000,000 horse-years). Reported risk factors of EMND (age, breed) and other extraneous factors (sex, month of diagnosis) could not explain the observed geographic variations of disease rates. Nevertheless, there is evidence of some confounding attributable to age and breed. CONCLUSIONS: Although the mechanism responsible for the clustering of EMND in northeastern states is still unexplained, it is not an epiphenomenon caused by regional differences in the distribution of the factors investigated.
Animals↗
Optimizing inhaled drug delivery in patients with asthma.
Successful management of asthmatic patients depends on achieving adequate delivery of inhaled drugs to the lung. This assumes particular importance for inhaled corticosteroids where the therapeutic goal should be to achieve a high ratio of airway anti-inflammatory efficacy to local and systemic side effects. The availability of user-friendly inhaler devices requires a critical appraisal of their effectiveness and an evaluation of whether improved lung deposition of anti-asthma drugs translates into improved clinical efficacy. There is evidence to suggest that the routine use of large-volume spacers for inhaled corticosteroids may not be the best first-line option, in that reduced drug delivery is associated with multiple actuations, inhalation delay and the presence of static electricity. Breath-actuated pressurized aerosol devices or dry powder inhaler devices may be a better option for many asthmatic patients, although the efficiency of drug delivery varies considerably between these devices. There is good evidence with a reservoir dry powder inhaler device to show that improved lung deposition translates into better therapeutic response, both in terms of beta 2-agonist and corticosteroid delivery. For inhaled corticosteroids, such as fluticasone propionate and budesonide, there is evidence to show that systemic bioactivity is mainly determined by lung bioavailability rather than gastrointestinal bioavailability, because of the absence of first-pass metabolism of these drugs in the lung. There is also evidence to show that the greater glucocorticoid potency of fluticasone propionate translates directly into greater systemic bioactivity, but not into enhanced efficacy, at doses above 1 mg daily. The use of efficient delivery systems, such as the reservoir dry powder inhaler device, may not only improve control of asthma and compliance with therapy, but may also allow dose reduction ('step-down' therapy) and hence may possibly reduce overall prescribing costs in the long term.
Anti-Asthmatic Agents↗
Size exclusion chromatography.
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Calibration↗
CD8 cells play a critical role in delayed type hypersensitivity to intact Cryptococcus neoformans.
Although cell-mediated immunity is critical for optimal host defense to C. neoformans, the role of T lymphocyte subsets is complex and poorly understood. CD8 cells are important both for optimal host defense against C. neoformans, and for expression of delayed type hypersensitivity (DTH). Because host defense correlates with the ability to mount a DTH response to C. neoformans, the current studies were performed to determine the mechanism by which CD8 cells participate in DTH. Mice were immunized by the intratracheal route with live C. neoformans, or by the subcutaneous route with heat-killed C. neoformans. Mice were depleted of CD8 cells in vivo by administration of mAb. After challenge with soluble cryptococcal Ag, the DTH response was quantified as footpad swelling. We found that mice depleted of CD8 cells before immunization were unable to express DTH. Mice depleted of CD8 cells after immunization but before challenge also were unable to express DTH. Splenocytes of mice depleted of CD8 cells in vivo, before immunization, failed to transfer DTH to naive, undepleted mice. Immune splenocytes depleted of CD8 cells in vitro also failed to transfer DTH to naive, undepleted mice. These data indicate that CD8 cells were necessary during the challenge and immunizing phases of DTH, and were necessary for expression of DTH. However, CD8 cell depletion did not abrogate DTH in mice immunized with either soluble cryptococcal Ag in complete Freund's adjuvant, or sheep red blood cells, which are mediated by CD4 cells. These data suggest that CD8 cells play a critical role in the cell-mediated immune response to C. neoformans. Based on this information, it may be possible to protect hosts with deficiencies of CD4 cells, such as in AIDS, by designing immunizing strategies for stimulating CD8 cells.
Animals↗
Women in management. Why women in the NHS don't get a share of the action.
The survey was designed to give a representative picture of staff attitudes across the South East Thames region. A key intention of the survey was to collect information from all staff groups and locations. Questionnaires were sent out during September and October 1992 to a random sample of women and men. By the close of the survey, 1,886 usable questionnaires had been returned from members of the survey sample, representing a response rate of 43 per cent. In addition, 512 questionnaires had been received from volunteers. The analysis presented in the report is based on 2,398 survey respondents, 18 per cent of whom were men.
Administrative Personnel↗
The neurotrophins NT-4/5 and BDNF augment serotonin, dopamine, and GABAergic systems during behaviorally effective infusions to the substantia nigra.
Brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) have both been identified as ligands for the TrkB receptor, yet differences have emerged in terms of their in vitro potencies for neuronal survival and differentiation. This has prompted the in vivo study of their effects on behavior and neuro-chemical parameters associated with dopamine, serotonin, and GABAergic neurons in the basal ganglia. Two-week supranigral infusions of NT-4/5 and BDNF were similar in their ability to augment levels of the dopamine metabolite homovanilic acid (HVA) (63 and 78%, respectively) and the ratios of dihydroxphenylacetic acid/dopamine (DOPAC/DA) (39, 48%) and HVA/DA (85, 77%) in the caudate-putamen of the hemisphere ipsilateral to the nigral infusion. Striatal concentrations of DOPAC were elevated 45% by BDNF but not by NT-4/5. The 3-MT/dopamine ratio, an indicator of dopamine release, was elevated by 38 and 32% in the striata of BDNF- and NT-4/5-infused rats, respectively. Striatal indoleamine metabolism, determined by the ratio of 5-hydroxyindoleacetic acid (5HIAA)/serotonin was also elevated by NT-4/5 and BDNF in the caudate-putamen (29, 32%), and the 5HIAA content of the substantia nigra was elevated by both factors (43, 40%). The activity of GAD within the superior colliculus was elevated 21 and 41% by BDNF and NT-4/5, respectively. A contraversive rotational bias was induced in BDNF and NT-4/5-treated rats challenged with d-amphetamine, and these responses were blocked by pretreatment with selective D1 or D2 receptor antagonists but not by opiate receptor antagonism. Thus, NT-4/5 and BDNF can elevate the turnover of dopamine through both metabolic and release pools and augment the behavioral response to d-amphetamine. The role for dopamine in this behavioral response is indicated by the requirement of unoccupied D1 and D2 receptors, but may also involve changes in serotonergic, GABAergic, or other pathways. The TrkB receptor-specific actions of BDNF and NT-4/5 may have implications for understanding the etiology or treatment of basal ganglia disorders.
Animals↗
In vivo depletion of murine CD8 positive T cells impairs survival during infection with a highly virulent strain of Cryptococcus neoformans.
Cell-mediated immunity plays an important but incompletely understood role in host defense against Cryptococcus neoformans. Because of their multiple capacities as cytokine-secreting cells, cytotoxic cells, and antigen-specific suppressor cells, CD8 positive T lymphocytes could potentially either enhance or impair host defense against C. neoformans. To determine whether CD8 T cells enhance or inhibit host defence during an infection with a highly virulent strain of C. neoformans, we examined the effect of in vivo CD8 cell depletion on survival and on the number of organisms in mice infected by either the intratracheal or intravenous routes. Adequacy of depletion was confirmed both phenotypically and functionally. Regardless of the route of infection, we found that survival of mice depleted of CD8 T cells was significantly reduced compared to undepleted mice. Surprisingly, however, CD8 depletion did not alter organism burden measured by quantitative CFU assay in mice infected by either route. These data demonstrate that CD8 positive T cells participate in the immune response to a highly virulent strain of C. neoformans. By contrast to minimally virulent isolates that do not cause a life threatening infection, the immune response to a highly virulent isolate does not alter the burden of organisms, but does enhance host defense as it is necessary for the optimal survival of infected mice.
Animals↗
Efficacy of brain-derived neurotrophic factor and neurotrophin-3 on neurochemical and behavioral deficits associated with partial nigrostriatal dopamine lesions.
Brain-derived neurotrophic factor (BDNF) promotes the survival of dopamine (DA) neurons, enhances expression of DA neuron characteristics, and protects these cells from 6-hydroxydopamine (6-OHDA) toxicity in vitro. We tested the ability of BDNF or neurotrophin-3 (NT-3) to exert similar protective effects in vivo during chronic delivery of 6-OHDA to the rat neostriatum. Chronic infusions of BDNF or NT-3 (12 micrograms/day) above the substantia nigra were started 6 days before and continued during an 8-day chronic intrastrial infusion of 6-OHDA. In control and neurotrophin-treated animals, 6-OHDA treatment selectively depleted 50-60% of nigrostriatal DA nerve terminals but produced little if any loss of pars compacta DA cell bodies. This partial DA lesion resulted in three rotations per minute toward the lesioned hemisphere after treatment with the DA release-inducing drug d-amphetamine. Compared with supranigral infusions of vehicle, BDNF and NT-3 decreased the number of these ipsiversive rotations by 70 and 48% and increased by 20- and 10-fold, respectively, the number of contraversive rotations observed after amphetamine injection. When challenged with the DA receptor agonist apomorphine, BDNF- and NT-3-treated animals also exhibited a seven- and 3.5-fold increase in the number of contraversive rotations relative to the vehicle group, respectively. Compared with vehicle, BDNF increased striatal levels of homovanillic acid (HVA; 86%), 3,4-dihydroxyphenylacetic acid (DOPAC; 42%), and 5-hydroxyindoleacetic acid (5-HIAA; 32%) and the HVA/DA (43%) and 5-HIAA/serotonin (34%) ratios in the DA-denervated striatum. NT-3 augmented only striatal 5-HIAA levels (24%). Neither factor altered the 6-OHDA-induced decrease in striatal DA levels or high-affinity DA uptake and thus did not protect against the destruction of DA terminals and did not alter striatal D1 or D2 ligand binding. Choline, GABA, and glutamate uptake in the striatum were not altered by the lesion or neurotrophin treatment. Thus, BDNF and to a lesser extent NT-3 reverse rotational behavioral deficits and augment striatal DA and 5-HT metabolism in a partial DA lesion model.
3,4-Dihydroxyphenylacetic Acid↗
The capacity-building approach to intervention maintenance implemented by the Stanford Five-City Project.
Increasingly, agencies supporting community health promotion interventions require participating communities and evaluators to specify how the intervention will be maintained once agency funding ends. The Stanford Five-City Project (FCP) implemented two different strategies to maintain its heart disease education program, with the second strategy designed to overcome the barriers to implementation that were encountered by the first. This paper provides a practice-oriented description of the initial 'community network' maintenance strategy of the FCP, the barriers that were encountered as this network strategy was implemented, the alternative 'capacity-building' strategy directed at local health educators and the successful implementation of this alternative. Also discussed are the community organization issues underlying the shift in intervention maintenance strategies and the specific components of the capacity-building strategy, including its focus on health educators, and its application of a training of trainers model and cooperative learning methods to provide professional development, technical assistance and other resources to a target group of community health educators. Our experience indicates that capacity-building is a viable method for intervention maintenance and that it may also facilitate efforts to disseminate model health promotion programs to communities lacking experience in community health promotion intervention.
California↗
Pharmacokinetics and pharmacodynamics of intraspinal dexmedetomidine in sheep.
INTRODUCTION: Epidural and spinal injection of alpha 2-adrenergic agonists causes analgesia and hypotension. For opioids, relative analgesic potency of epidural to intravenous administration decreases with increasing lipophilicity, but such pharmacodynamic studies have been performed with only one alpha 2-adrenergic agonist, clonidine, of moderate lipophilicity. This study examines antinociception, transfer to cerebrospinal fluid (CSF), and CSF pharmacokinetics in sheep of the selective alpha 2-adrenergic agonist dexmedetomidine, with lipophilicity 3.5 times greater than clonidine, and correlates CSF concentrations to hemodynamic effects. METHODS: Six sheep with chronically implanted epidural, intrathecal, and vascular catheters received, on separate days, 100 micrograms dexmedetomidine intravenously, epidurally, or intrathecally. Cerebrospinal fluid and blood were sampled at specified intervals for dexmedetomidine assay. Pharmacokinetics of dexmedetomidine in CSF were determined using a NONMEM approach. Hemodynamic effects were measured and correlated to CSF concentrations. A second group of four sheep received intrathecal dexmedetomidine to define its time course for antinociception. RESULTS: Intrathecal dexmedetomidine decreased blood pressure within 1 min, with a maximum reduction of -22 +/- 3%. Epidural injection decreased blood pressure with a slower onset (11 min) and to a lesser degree (-14 +/- 4%), whereas intravenous injection did not affect blood pressure (-8 +/- 6%). Dexmedetomidine absorption in CSF after epidural injection was rapid (Tmax = 5-20 min), although pharmacokinetic modeling suggested a biphasic absorption process. Only 22% of the injected dose was identified in the CSF. There was a delay of at least 30 min between peak CSF concentrations and time of maximal reduction in blood pressure. At times of identical CSF dexmedetomidine concentrations, blood pressure decreased more after epidural than after intrathecal administration. Intrathecal dexmedetomidine injection produced maximum antinociception within 20-30 min of injection. CONCLUSIONS: These data support a primary spinal site of action for decreased blood pressure after intraspinal dexmedetomidine injection. Dexmedetomidine appears rapidly in CSF after epidural administration and decreases blood pressure. The relationship between CSF dexmedetomidine concentrations and drug effect may require more complex modeling tools than those used to relate plasma drug concentrations to effects of systemically administered opioids or neuromuscular blockers.
Adrenergic alpha-Agonists↗
Sarcoidosis: recurrence of primary disease in transplanted lungs.
PURPOSE: To assess findings of recurrent disease on thin-section computed tomographic (CT) studies and results of bronchoalveolar lavage and transbronchial biopsy (BAL-TBB) procedures performed in adult lung transplant recipients. MATERIALS AND METHODS: Between 1990 and 1993, 32 single-lung, 14 double-lung, and three heart-lung transplantation procedures were performed in 47 patients; 176 thin-section CT scans were reviewed, with a mean follow-up of 18.9 months after transplantation. RESULTS: Sarcoidosis was diagnosed after BAL-TBB of the lung allografts 3 and 15 months after transplantation in both patients without symptoms who received transplants for treatment of sarcoidosis. In one patient, diffuse miliary nodules seen on chest radiographs and thin-section CT scans disappeared after administration of an increased dose of corticosteroids; in the other patient, no radiologic finding of sarcoidosis was present. No recurrence was seen in patients who received transplants for treatment of other diseases. CONCLUSION: Recurrence of primary disease should be considered whenever abnormalities are seen on chest radiographs or thin-section CT scans. Sarcoidosis may recur with or without radiologic findings after transplantation.
Adolescent↗
Authoritative parenting, child competencies, and initiation of cigarette smoking.
School-based social influence programs to prevent adolescent smoking are having limited success in the long term. Intervening earlier in the process of smoking onset, during the childhood years, may be required to prevent adolescent smoking. Child socialization variables, specifically parenting behaviors and child competencies, may be important to understanding the earliest phase of smoking onset. This study tested hypotheses of association between authoritative parenting behaviors, enhanced child competencies, and relatively low rates of initiation of cigarette smoking. Analyzing cross-sectional survey data from 937 students in Grades 3 to 8, we found general support for the study hypotheses: Authoritative parenting was positively associated with child competencies; children's competency levels were inversely related to their rates of smoking intention, initiation, and experimentation; authoritative parenting was inversely related to rates of child smoking intention and behaviors; and authoritative parenting and parent smoking status had independent associations with child initiation of cigarette smoking. These results indicate that child socialization variables merit further investigation for their potential role in the development of early intervention programs for smoking prevention.
Adolescent↗
Child health. Achieving balance.
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Child↗
Strelley: teamworking for health.
Strelley nursing development unit has won national recognition for its pioneering work in exploring new models of health visiting, and the role of the public health visitor in particular. Catherine Jackson talks to team members about the fruits of reflective practice.
Clinical Nursing Research↗
New world, new dilemmas.
Department of health policy to integrate health visitors and district nurses with the primary health care team raises critical professional and management issues. But pilot schemes have revealed serious flaws in direct management by GPs of attached community nursing staff. Catherine Jackson reports.
Community Health Nursing↗