Trend analysis of socioeconomic differentials in deaths from injury in childhood in Scotland, 1981-95.
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Adolescent↗
Biomedical subjects
A Morrison
Publications and source records attributed to A Morrison.
Inhibition of influenza virus infections in mice by GS4104, an orally effective influenza virus neuraminidase inhibitor.
The carbocyclic transition state sialic acid analog GS4071 ([3R,4R,5S]-4-acetamido-5-amino-3-[1-ethylpropoxy]-1-cyclohexane-1 -carboxylic acid), a potent influenza virus neuraminidase inhibitor, was highly inhibitory to influenza A/NWS/33 (H1N1), A/Victoria/3/75 (H3N2), A/Shangdong/09/93 (H3N2) and B/Hong Kong/5/72 viruses in Madin Darby canine kidney (MDCK) cells. The 50% effective concentrations in these experiments ranged from 1.8 to 59.5 microM, with no cytotoxicity evident at 1000 microM, using inhibition of viral cytopathic effect determined visually and by neutral red dye uptake. The ethyl ester prodrug of GS4071, GS4104, administered by oral gavage (p.o.), had significant inhibitory effects on infections in mice induced by these viruses. Antiviral effects were seen as prevention of death, increase in mean day to death, inhibition of decline of arterial oxygen saturation, lessened lung consolidation and inhibition of infectious virus recovered from the lungs. No toxicity was seen in dosages up to 100 mg/kg/day (highest evaluated). Comparison experiments run versus the influenza A (H1N1) virus-induced infection using GS4104, GS4071 and the neuraminidase inhibitor zanamivir (GG167, 4-guanidino-Neu5Ac2en), all administered p.o., indicated a 10-fold or greater potency for inhibiting the infection by GS4104. The minimum effective dosage for GS4104 was 0.1 mg/kg/day, with the compound administered twice daily for 5 days beginning 4 h pre-virus exposure. Oral therapy with GS4104 could be delayed from 48 to at least 60 h after exposure of mice to influenza A (H1N1) virus and still render a significant antiviral effect, the time of delay being dependent on the viral challenge dose. Intranasal instillation of GS4071 and GG167 to mice infected with influenza virus was highly inhibitory to the infection, the minimum effective dosages to significantly prevent death being 0.01 mg/kg/day for GS4071 and 0.1 mg/kg/day for GG167. Caging of infected mice treated with 10 mg/kg/day of GS4104 with infected saline-treated animals did not transfer any influenza-inhibitory effect to the latter animals. These data provide strong evidence of the potential of orally administered GS4104 for treatment of influenza A and B virus infections in humans.
Acetamides↗
Developing injury surveillance in accident and emergency departments.
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Child↗
Injury surveillance in accident and emergency departments: to sample or not to sample?
OBJECTIVES: To establish whether injury surveillance based on sampling strategies is as valid as total patient surveillance. METHODS: Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) data for 1996 were retrospectively analysed using five sampling frames. Proportions for key variables were calculated for each sample, then compared with the proportions for the total population of patients. RESULTS: Two of the five sampling frames produced statistically significant differences from the total population, which can be explained by seasonal variations. However, no significant differences were observed between the remaining three samples and the total population. CONCLUSIONS: A well planned and executed sampling strategy can generate as valid data as total patient surveillance, obviating the need for data collection on every patient presenting with an injury or poisoning. In practice, however, systematic sampling can be difficult to implement and sustain, counterbalancing the economic advantages.
Adolescent↗
Australian Incident Monitoring Study in intensive care: local unit review meetings and report management.
The Australian Incident Monitoring Study in the intensive care unit (AIMS-ICU) is a national study established through nursing and medical collaboration to develop, introduce and evaluate an anonymous voluntary incident reporting system. To ensure incident monitoring results in improved patient safety, it is essential that reported incidents are followed up regularly. Local unit review meetings are an effective forum for discussion and review of reports amongst a wide group of practitioners from the intensive care unit (ICU). All staff should be invited to participate in order to suggest preventative strategies, report on incident follow up and explore national study findings. Ongoing momentum of the project is assisted by highlighting its positive contributions to patient care and safety via newsletters, poster displays and targeted correspondence. New staff require orientation to the reporting system and assurance regarding safety of data. The emphasis must focus on the system, not the individual.
Australia↗
Problems associated with nursing staff shortage: an analysis of the first 3600 incident reports submitted to the Australian Incident Monitoring Study (AIMS-ICU).
Although many studies have attempted to define appropriate nursing staff levels, allocation and patient dependency, minimal data is available on the effect of nursing staff shortage (NSS) on quality of care provided in intensive care. This study aimed to identify incidents associated with staff shortage as reported to the Australian Incident Monitoring Study-ICU (AIMS-ICU) project and to assess their estimated effect on patient outcome. A search of narrative keywords and contributing factors identified 89 nursing staff shortage incidents (NSS-INCIDENTS) and 373 incidents involving nursing staff shortage contributing factors (NSS-CF). NSS resulted from inappropriate rostering for current patient load (81%) and inability to respond to increased unit activity (19%). Most frequent associated incidents included problems with: drug administration/documentation (47), patient supervision (20), set-up of ventilators/equipment (16), and accidental extubation (14). Undesirable patient outcomes included: major physiological change (22%), patient/relative dissatisfaction (12%), and physical injury (3%). This study suggests that inadequate staffing results in incidents and compromised patient safety.
Australia↗
A novel, negative selectable marker for gene disruption in Dictyostelium.
The expression of an ochre suppressor mutant of the GluII(UUA) tRNA appears to be lethal to Dictyostelium, and offers a novel 'positive negative' strategy to select for targeted gene disruption by homologous recombination. Inclusion of the suppressor tRNA gene decreases the overall transformation frequency by approximately 20-fold. This increases the proportion of targeted gene disruptions to over 90%.
Animals↗
Positive cross-regulation and enhancer sharing: two mechanisms for specifying overlapping Hox expression patterns.
Vertebrate Hox genes display nested and overlapping patterns of expression. During mouse hindbrain development, Hoxb3 and Hoxb4 share an expression domain caudal to the boundary between rhombomeres 6 and 7. Transgenic analysis reveals that an enhancer (CR3) is shared between both genes and specifies this domain of overlap. Both the position of CR3 within the complex and its sequence are conserved from fish to mammals, suggesting it has a common role in regulating the vertebrate HoxB complex. CR3 mediates transcriptional activation by multiple Hox genes, including Hoxb4, Hoxd4, and Hoxb5 but not Hoxb1. It also functions as a selective HOX response element in Drosophila, where activation depends on Deformed, Sex combs reduced, and Antennapedia but not labial. Taken together, these data show that a Deformed/Hoxb4 autoregulatory loop has been conserved between mouse and Drosophila. In addition, these studies reveal the existence of positive cross-regulation and enhancer sharing as two mechanisms for reinforcing the overlapping expression domains of vertebrate Hox genes. In contrast, Drosophila Hox genes do not appear to share enhancers and where they overlap in expression, negative cross-regulatory interactions are observed. Therefore, despite many well documented aspects of Hox structural and functional conservation, there are mechanistic differences in Hox complex regulation between arthropods and vertebrates.
Animals↗
A volumetric study of measurements and calculations of lung density corrections for 6 and 18 MV photons.
PURPOSE: For treatment of lung cancer, dose heterogeneity corrections and subsequent prescription alteration remain controversial. Previous dosimetry studies based on slab geometry with a single beam geometry do not represent the clinical situation. A circumscribed tumor within lung poses a more complex problem. Energy choice also remains controversial. METHODS AND MATERIALS: An anthropomorphic phantom was modified by replacing lung cylinders (2.5 and 5.0 cm diameters by 5.0 cm length) with muscle-equivalent cylinders. The phantom was scanned on a CT simulator. Gross, clinical, and planning target volumes (GTV, CTV, PTV1 including tumor and regional nodes, PTV2 including tumor only) were designated slice-by-slice. Three-dimensional planning was performed with large fields (AP/PA/RPO) covering PTV1 and boost fields optimized for each PTV2, for 6 and 18 MV photons. Homogeneous, Ratio-Tissue-Air-Ratio (RTAR), and convolution-adapted RTAR (CARTAR) calculation algorithms were tested. Film was placed between phantom slices at the "tumor" levels. The phantom was irradiated with monitor units corresponding to homogeneous calculations, based on a homogeneous prescription. Measured and calculated doses were compared by isodoses and dose volume histograms. Ionization chambers and TLDs were also used for some test cases. RESULTS: The measured minimum dose covering PTV2 was within 5% of the homogeneous prescription dose of 70 Gy for 6 MV photons, while a lower dose (89% of prescription dose) was measured for 18 MV. The algorithms overpredicted the minimum dose to PTV2 by 6-18%. If the monitor units had been reduced according to simplistic heterogeneous calculations, the small PTV2 would have only been covered by 58 Gy for 18 MV irradiation. Based on this, a clinician may opt to actually increase the prescribed dose, thereby offsetting decreased monitor units. None of the algorithms predicted the diffuse penumbra associated with 18 MV photons in lung. CONCLUSION: Before adjusting dose prescriptions based on heterogeneity corrections, realistic phantom studies must be performed. The accuracy and effect of the corrections must then be assessed. The deficient coverage of PTV2 by the 18 MV beam compares unfavorably with the slight increase (5%) in hot spots associated with 6 MV. Our studies support strong caution before reducing dose prescriptions based on simple algorithms.
Algorithms↗
Elements both 5' and 3' to the murine Hoxd4 gene establish anterior borders of expression in mesoderm and neurectoderm.
In this report, we show that a lacZ reporter spanning 12.5 kb of murine Hoxd4 genomic DNA contains the major regulatory elements controlling Hoxd4 expression in the mouse embryo. Mutational analysis revealed multiple regulatory regions both 5' and 3' to the coding region. These include a 3' enhancer region required for expression in the central nervous system (CNS) and setting the anterior border in the paraxial mesoderm, and a 5' mesodermal enhancer that directs expression in paraxial and lateral plate mesoderm. A previously defined retinoic acid response element (RARE) is a component of the 5' mesodermal enhancer. Our results support a model in which retinoic acid receptors (RARs) and HOX proteins mediate the initiation and maintenance of Hoxd4 expression.
Animals↗
Zidovudine adherence in persons with AIDS. The relation of patient beliefs about medication to self-termination of therapy.
OBJECTIVE: To examine the relation of patient beliefs about medication usage and adherence to zidovudine (ZDV) therapy in persons with AIDS. DESIGN: Face-to-face interviews were used to determine attitudes of persons with AIDS toward ZDV and other prescribed medications, history of ZDV usage, and sociodemographics. SETTING: A public hospital infectious disease clinic, an AIDS day care program, and an inpatient unit in a voluntary hospital where care was provided cooperatively by staff and an informal-care partner. PATIENTS/PARTICIPANTS: One hundred forty-one people with the acquired immunodeficiency syndrome agreed to be reinterviewed as part of a longitudinal, New York City-based study examining outcomes related to quality of life. Initial recruitment procedures were to approach all active AIDS patients at each of the three sites between January and July of 1992: reinterviews, which were conducted an average of 6 months later, occurred from mid-1992 through May of 1993. MEASUREMENTS AND MAIN RESULTS: The Zidovudine Drug Attitude Inventory was used to assess subjective feelings and attitudes concerning ZDV and prescribed medications in general. Respondents were grouped into five categories on the basis of their ZDV usage history: (1) "short-term" users (i.e., those who had been taking ZDV for 25 months or less); (2) "long-term" users (i.e., those who had been taking ZDV for more than 25 months); (3) self-terminated users; (4) doctor-terminated users; and (5) never users. Long-term users were likely to view ZDV as an illness prophylactic. In contrast, self-terminated users and never users were most likely to believe that ZDV caused adverse side effects and that medicine need not be taken as prescribed. CONCLUSIONS: Patients' beliefs about ZDV were significantly associated with adherence-related behavior. In particular, those who had self-terminated ZDV treatment believed that taking the drug was harmful, were skeptical of its ability to prevent illness, and felt that physician's directives about medication usage in general could be disregarded. These findings highlight the importance of educating patients about ZDV and of establishing regular patient-clinician exchanges concerning patient's experience with and beliefs concerning ZDV.
Acquired Immunodeficiency Syndrome↗
The Sexual Health Help Centre: a service for young people.
BACKGROUND: The Sexual Health Help Centre (SHHC) was opened in 1995 to provide treatment, advice and information on family planning and sexual health issues for young people under the age of 20 years, in a way which is open and non-threatening. This paper describes an evaluation conducted during the first 9 months of service operation. METHODS: Young people's experience of the SHHC were elicited, and compared with their experiences of conventional family planning services in Glasgow. RESULTS: The SHHC has been successful in attracting young people for help with family planning problems and provides a more acceptable environment than conventional family planning services. However, a greater number of young men and young people under the age of 16 should be encouraged to attend the service. CONCLUSION: Young people are more likely to visit family planning services if they are offered a wide range of family planning and sexual health services in a non-judgmental, non-threatening environment.
Adolescent↗
A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore Longitudinal Study of Aging.
Previous reports have suggested that estrogen replacement therapy (ERT) in women may exert a protective effect on their risk of developing Alzheimer's disease (AD). We investigated this relationship in the Baltimore Longitudinal Study of Aging (BLSA), a prospective multidisciplinary study of normal aging conducted by the National Institute on Aging. The sample consisted of 472 post- or perimenopausal women followed for up to 16 years in the BLSA. We documented ERT prospectively at each BLSA visit, and we categorized women who had used oral or transdermal estrogens at anytime as ERT users. We used Cox proportional hazards models with time-dependent covariates to estimate the relative risk of developing AD after ERT as compared with women who had not used estrogen replacement. Approximately 45% of the women in the cohort had used ERT, and we diagnosed 34 incident cases of AD (NINCDS/ADRDA criteria) during follow-up, including nine estrogen users. After adjusting for education, the relative risk for AD in ERT users as compared with nonusers was 0.46 (95% CI, 0.209-0.997), indicating a reduced risk of AD for women who had reported the use of estrogen. Our data did not show an effect for duration of ERT usage. Our finding offers additional support for a protective influence of estrogen in AD. Randomized clinical trials are necessary to confirm this association, which could have significant public health impact.
Adult↗
HOXD4 and regulation of the group 4 paralog genes.
From an evolutionary perspective, it is important to understand the degree of conservation of cis-regulatory mechanisms between paralogous Hox genes. In this study, we have used transgenic analysis of the human HOXD4 locus to identify one neural and two mesodermal 3' enhancers that are capable of mediating the proper anterior limits of expression in the hindbrain and paraxial mesoderm (somites), respectively. In addition to directing expression in the central nervous system (CNS) up to the correct rhombomere 6/7 boundary in the hindbrain, the neural enhancer also mediates a three rhombomere anterior shift from this boundary in response to retinoic acid (RA), mimicking the endogenous Hoxd4 response. We have extended the transgenic analysis to Hoxa4 identifying mesodermal, neural and retinoid responsive components in the 3' flanking region of that gene, which reflect aspects of endogenous Hoxa4 expression. Comparative analysis of the retinoid responses of Hoxd4, Hoxa4 and Hoxb4 reveals that, while they can be rapidly induced by RA, there is a window of competence for this response, which is different to that of more 3' Hox genes. Mesodermal regulation involves multiple regions with overlapping or related activity and is complex, but with respect to neural regulation and response to RA, Hoxb4 and Hoxd4 appear to be more closely related to each other than Hoxa4. These results illustrate that much of the general positioning of 5' and 3' flanking regulatory regions has been conserved between three of the group 4 paralogs during vertebrate evolution, which most likely reflects the original positioning of regulatory regions in the ancestral Hox complex.
Animals↗
Functional advantages of laparoscopic live-donor nephrectomy compared with conventional open-donor nephrectomy.
Live-donor kidney transplants accounted for only 27% of all kidney transplants performed in the United States in 1995. Prolonged hospitalization, pain, extended convalescence, and related socioeconomic concerns associated with traditional open-donor nephrectomy surgery may discourage potential donors, contributing to a low percentage of live kidney donors. To remove such disincentives, the laparoscopic live-donor nephrectomy procedure was introduced. In this study, the post-discharge course of 10 laparoscopic nephrectomy donors was compared with that of 27 open nephrectomy donors over the same time period. Laparoscopic nephrectomy donors experienced significantly shorter hospitalizations, less pain, felt able to return to work and normal routines sooner, and needed significantly less assistance during the recuperation period than did open nephrectomy donors. The laparoscopic nephrectomy procedure may decrease many of the concerns of potential donors, thus making live kidney donation more attractive and increasing the kidney supply.
Activities of Daily Living↗
Anaesthetists and the Calman proposals.
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Anesthesiology↗