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Biomedical subjects

M Stevenson

Publications and source records attributed to M Stevenson.

At least 127 records · Page 7Linked to original sources
PubMed1996

Increased plasma human immunodeficiency virus type 1 burden following antigenic challenge with pneumococcal vaccine.

Primary factors that influence virus burden during human immunodeficiency virus type 1 (HIV-1) disease progression remain a fundamental issue in pathogenesis. Because pneumococcal vaccine is routinely given to HIV-1-infected patients and replication of HIV-1 within CD4 T cells is dependent on the activation state of the cell, it was investigated whether the T cell activation that enhances the immune response to vaccines may also enhance HIV-1 replication. Vaccination of asymptomatic HIV-1-infected patients led to rapid and significant increases in virus burden in some patients. The magnitude of these increases correlated significantly with the extent of the antibody response to the vaccination. Thus, antigenic stimulation by vaccines designed to prevent secondary infections may promote HIV-1 replication in certain patients. These findings provide a window for examining HIV-1 pathogenesis and for determining the appropriate preventive measures against other diseases in HIV-1-infected persons.

Adult↗
PubMed1996

Regional variations in the utilization rate of vaginal and abdominal hysterectomies in the United Kingdom.

BACKGROUND: Large geographic variations in hysterectomy rates are well known; however, very little is known about geographic variations in the route of the procedure, i.e. whether it is performed abdominally or vaginally. We compared utilization rates for abdominal and vaginal hysterectomies for the 14 Regional Health Authorities of England, and Northern Ireland over a three-year period. METHODS: Data were collected in the form of hospital episode statistics and small area analysis techniques were used to document regional variations. RESULTS: Large regional differences in the utilization of vaginal hysterectomies were recorded. Three areas in particular (Northern Ireland, Yorkshire and NW Thames) displayed high vaginal to abdominal ratios. Northern Ireland recorded the highest ratio (0.366), Mersey Regional Health Authority the lowest (0.139). The use of the vaginal route was found to increase with age, and was the most common route for the > 65 years age group. CONCLUSION: Despite an increasing volume of evidence advocating the use of the vaginal route, there appears to be a resistance to its use, except in older women. The role of physician practice style, and in particular group clinical judgement, is highlighted as being significantly involved in explaining the observed geographic variations.

Adult↗
PubMed1996

A case-control study of childhood pedestrian injuries in Perth, Western Australia.

STUDY OBJECTIVES: To identify the determinants of childhood pedestrian injuries, taking the child's exposure to the road environment into account. DESIGN: This was a case-control study. SETTING AND PARTICIPANTS: The study was conducted in Perth, Western Australia between 1991 and 1993. Altogether 100 injured and 400 uninjured child pedestrians aged 1 to 14 years were studied. Aspects of the child's social and physical environments, measures of his or her behaviour, cognitive skills, and "habitual" exposure to the road environment, as well as his or her knowledge of road safety, were recorded. MAIN RESULTS: The likelihood of injury increased by 12% with each 10,000 vehicles per day increase in the volume of traffic (odds ratio (OR) 1.12, 95% confidence interval (CI) = 1.05, 1.19) on roads most frequently crossed. In addition, the presence of visual obstacles on the verge of the child's street of residence increased the likelihood of injury by more than 2.6 times (OR 2.68, 95% CI = 1.42, 5.02). In contrast, the absence of footpaths was associated with a 52% reduction in the likelihood of injury compared with the presence of footpaths on the child's street of residence (OR 0.48, 95% CI = 0.27, 0.87). CONCLUSION: The amount of exposure to the road environment and the nature of the road environment to which the child pedestrian was exposed partly influenced the likelihood of injury in children from low socioeconomic areas, male children, and children aged 13 to 14 years. Until now, the excess incidence of childhood pedestrian injuries in these subgroups of the population had not been explained because the child's exposure per se had not been examined.

Accidents, Traffic↗
PubMed1996

Aboriginal health in the peel region of Western Australia.

OBJECTIVE: A cross sectional survey of the Aboriginal people living in Mandurah, Pinjarra and Waroona (South West district of Western Australia) was undertaken to determine their health status and health service utilisation patterns. METHOD: The project was funded by the General Practice Research Program and conducted by the Forrest House Medical Group. The data were collected by an Aboriginal research assistant with tertiary training in public health. Demographic and health characteristics, prevalence of common acute and chronic conditions, rates of pregnancy, use of antenatal and women's health screening services, use of legal and illegal drugs, and satisfaction with local health services were estimated. RESULTS: A total of 57 families were interviewed, they comprised 271 adults and children. Acute and chronic health problems were common, the rate of pregnancy was high for young women, and the immunisation status was poor among children. Respondents were more likely to express satisfaction with the Aboriginal health worker and local doctor services than with the local hospital service. The local doctor's surgery was the most often used service. CONCLUSION: The survey included 70% of the Peel region's Aboriginal families and is one of the few comprehensive descriptions of the health status of an urban Aboriginal group. Thus it should provide an excellent basis for the re-orientation of health services and the development of environmental and educational interventions to improve the health status of the Aboriginal people living in the Peel region. An advisory committee has been formed to take action from the findings.

Adult↗
PubMed1995

Efficient synthesis of viral nucleic acids following monocyte infection by HIV-1.

The replication of human immunodeficiency virus type 1 in mononuclear phagocytes (blood monocytes, tissue macrophages, and dendritic cells) is an important feature of HIV-1 pathogenesis. Although most primary HIV-1 isolates are able to productively infect monocytes, some reports suggest that rates of viral DNA synthesis and virus replication are reduced in HIV-1-infected monocytes as compared to infected T cells. In this study we compare kinetics of viral DNA synthesis in CD4+ T cells and monocytes following HIV-1 infection. Our results indicate that reverse transcription of viral nucleic acids following infection of monocytes occurs at rates equal to or greater than that observed following infection of T cells. These studies reveal no postentry restrictions to HIV-1 replication following infection in monocytes. Moreover, the results support the notion that both monocytes and CD4+ T cells are equally permissive for virus replication in infected individuals.

Cells, Cultured↗
PubMed1995

Molecular basis of cell cycle dependent HIV-1 replication. Implications for control of virus burden.

Research is beginning to yield insight into determinants which govern cell cycle dependence of provirus establishment by the onco-retroviruses. In the case of HIV-1, nucleophilic components associated with the viral preintegration complex facilitate mitosis independent nuclear localization of viral DNA and provirus establishment. Differences in the metabolic activity between G0 T cells and macrophages, the two primary targets for HIV-1 infection, lead to significantly different outcomes with regards to provirus establishment following infection of these cells. Thus, macrophages appear fully permissive to productive HIV-1 replication while non-dividing (G0 T cells) restrict virus replication at a step which proceeds nuclear import of viral DNA. The requirement for T cell activation in productive HIV-1 replication has important implications for the relationship between immune activation and virus burden. It remains to be determined whether modulating the immune activation status of the infected individual may provide an opportunity for modulating virus burden and influencing disease course.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Motor vehicle occupant injuries in children 2 years and younger: a comparison between Western Australia and New South Wales 1982-92.

OBJECTIVES: To compare the age specific rate of passenger injury and associated restraint use for children 2 years and younger in the state of Western Australia (WA), with the state of New South Wales (NSW), Australia for the period 1982-92. SETTING: The states of WA and NSW, Australia. METHODS: A descriptive retrospective study of child passenger injuries in WA and NSW was conducted for the period 1 January 1982 to the 31 December 1992. The data provided information about the injured child, such as sex and restraint use, the driver, vehicle, and collision factors, such as time and posted speed limit. RESULTS: A total of 2280 children aged 0 to 2 years were injured in motor vehicle collisions during the study period. Of these children, 653 were from WA and 1627 from NSW. Both the injury and mortality rates were higher in WA compared with NSW over the study period. However 80% and 79% of child passengers injured in WA and NSW, respectively, were restrained at the time of injury. Thus both the sex of the driver and the year the motor vehicle was manufactured best predicted the likelihood of a child being restrained. CONCLUSIONS: As at 1992, WA's population age specific passenger injury rate for children 0-2 years was more than twice the rate in NSW. The comparable rate of reported restraint use by injured children 0-2 years in WA and NSW suggests that non-use of restraints cannot be singled out as the most likely cause of WA's comparatively high rate of injury. It is difficult to determine whether the disparity in rates could be explained by the child passenger's exposure to crash risk factors, as little is known about child passenger levels of exposure to these factors. Further research is needed to address this issue.

Accidents, Traffic↗
PubMed1995

Computer-assisted decision support systems for patient management in an intensive care unit.

The application of the intelligent monitoring techniques of case-based reasoning and neural network analysis to physician decision making concerning patient care in an Intensive Car Unit (ICU) is described. Case-based reasoning offers a model for quickly matching--using a predetermined hierarchical structure--a single patient's parameters (text or numeric) to similar parameters contained in a clinical database. The output produces a group of patients which may be set to match exactly on certain characteristics and may also be set to match "as closely as possible" on a gradient of patient properties. Clinicians may thus use the system to find the group of the closest matching cases to their current patient. Aspects of the ICU history of the selected group may then be displayed graphically (e.g., mortality, length of stay, hours of ventilation, procedures utilized, and complications encountered). Neural network analysis is a pattern recognition technique which uses a training set of patient data (text or numeric) to seek mathematical relationships between various subsets of patient parameters. The discovered relationships from the training set are then applied to estimate the outcomes (e.g., mortality, length of stay, hours of ventilation) of new patients. The effects of these intelligent monitoring techniques are scheduled to be tested in a field trial held in a regional referral center ICU.

Algorithms↗
PubMed1994

The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells.

The replication of human immunodeficiency virus type 1 (HIV-1) in nondividing host cells such as those of macrophage lineage is an important feature of AIDS pathogenesis. The pattern of HIV-1 replication is dictated, in part, by the nucleophilic property of the viral gag matrix (MA) protein, a component of the viral preintegration complex that facilitates nuclear localization of viral nucleic acids in the absence of mitosis. We now identify the accessory viral protein Vpr, as a second nucleophilic component that influences nuclear localization of viral nucleic acids in nondividing cells. Reverse transcription and nuclear localization of viral nucleic acids following infection of cells by viruses lacking Vpr or viruses containing mutations in a gag MA nuclear localization sequence were indistinguishable from the pattern observed in cells infected by wild-type HIV-1. These viruses retained the ability to replicate in both dividing and nondividing host cells including monocyte-derived macrophages. In contrast, introduction of both gag MA and Vpr mutations in HIV-1 attenuated nuclear localization of viral nucleic acids in nondividing cells and virus replication in monocyte-derived macrophages. These studies demonstrate redundant nucleophilic determinants of HIV-1 that independently permit nuclear localization of viral nucleic acids and virus replication in nondividing cells such as monocyte-derived macrophages. In addition, these studies provide a defined function for an accessory gene product of HIV-1.

Base Sequence↗
PubMed1994

Cellular and viral determinants that regulate HIV-1 infection in macrophages.

Macrophages in brain, lung, and lymphatics constitute a major HIV reservoir during subclinical infection and disease. During HIV transmission macrophages are seemingly one of the first cells infected, being as efficient as T cells in supporting productive viral replication. Macrophages control a myriad of cell-mediated immune responses that regulate the levels of infection and lead to viral persistence. HIV determinants control viral entry and productive replication and, taken together with cellular differentiation factors, decide the outcome of virus-macrophage interactions. Most important, many clinical manifestations of HIV infection such as encephalitis, myelopathy, pneumonitis, and lymphadenopathy are closely linked to viral replication. Indeed, tissue pathology often correlates with viral gene expression in tissue macrophages. Taken together, these observations provide strong support for a central role of macrophages in progressive HIV infection and its clinical manifestations.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Inhibition of gp120-CD4 interaction and human immunodeficiency virus type 1 infection in vitro by pyridoxal 5'-phosphate.

Pyridoxal 5'-phosphate and related compounds were tested for their ability to inhibit gp120-CD4 interaction and human immunodeficiency virus infection in vitro. The results show that pyridoxal 5'-phosphate is a unique CD4 antagonist whose antiviral potency derives from the presence of both lysine-reactive and anionic substituents.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Alpha interferon-induced antiretroviral activities: restriction of viral nucleic acid synthesis and progeny virion production in human immunodeficiency virus type 1-infected monocytes.

Alpha interferon (IFN-alpha) restricts multiple steps of the human immunodeficiency virus type 1 (HIV-1) life cycle. A well-described effect of IFN-alpha is in the modulation of viral nucleic acid synthesis. We demonstrate that IFN-alpha influences HIV-1 DNA synthesis principally by reducing the production of late products of reverse transcription. The magnitude of IFN-alpha-induced downregulation of HIV-1 DNA and/or progeny virion production was dependent on the IFN-alpha concentration, the duration of cytokine administration, the multiplicity of infection, the viral strain, and the cycles of viral infection. Interestingly, reductions in viral DNAs could not fully account for the observed IFN-alpha-induced abrogation of progeny virion production. These data, by our investigation of both single-cycle and spreading viral infections, support a predominant but not exclusive effect of IFN-alpha on viral DNA synthesis.

Cells, Cultured↗
PubMed1994

Reduced nuclear import of human immunodeficiency virus type 1 preintegration complexes in the presence of a prototypic nuclear targeting signal.

Nuclear import of the retroviral preintegration complex and integration of retroviral with host cell DNA are essential steps for completion of the virus life cycle. The preintegration complex of the lentivirus human immunodeficiency virus type 1 (HIV-1) displays karyophilic properties and, as a consequence, is rapidly directed to the host cell nucleus by an energy-dependent transport pathway. The karyophilic properties of nuclear proteins are governed by a nuclear localization sequence, the targeting function of which can be inhibited in the presence of excess targeting signals. Here we present evidence that the nuclear import of a large karyophile--the preintegration complex of HIV-1--is inhibited in the presence of a prototypic nuclear targeting signal of simian virus 40 T antigen. This points to a novel strategy which prevents establishment of the provirus by interrupting nuclear localization of HIV-1 DNA.

Amino Acid Sequence↗
PubMed1994

Effect of hosiery on skin temperature in spastic quadriplegia. A preliminary study.

The effect of hosiery on 21 patients with spastic quadriplegia was studied by examining skin temperatures before and after wearing control socks (cotton or cotton/acrylic), compared with the test socks (21% stretch nylon and 80% synthetic hollow-core fiber). The latter are claimed by the manufacturers to provide superior warmth. Other investigations suggest that no material for a given thickness has superior insulation properties. The results of this preliminary study support these investigations, in that no significant difference in skin temperatures was found between the control and test socks when worn by this population.

Foot↗
PubMed1994

[Cervicitis--epidemiological and clinical risk for Chlamydia trachomatis infection in university students].

Fifty volunteer, asymptomatic sexually active university female students were examined and inquired, in order to find risk factors predictive of Chlamydia trachomatis infection. Epidemiologic and behavioral factors (age, number of sexual partners, oral contraceptives use and history of previous sexually transmitted diseases) were found to be similar among the studied group and published data for North American female college students, but barrier contraceptive methods use was found to be different. Twenty two per cent of the sample had clinical cervicitis, and 30% had subclinical. If the screening models proposed by different authors would have been applied, between a 32% and 72% of the sample would have been selectively for the presence of Chlamydia trachomatis. It is concluded that international sugerences about Chlamydia trachomatis screening should be adopted until national experiences are made.

Adult↗