Spread and prevention of some common viral infections in community facilities and domestic homes.
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Biomedical subjects
Publications and source records attributed to J Barker.
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Invasion plasmid antigen C (IpaC) is secreted via the type III secretion system (TTSS) of Shigella flexneri and serves as an essential effector molecule for epithelial cell invasion. The only homologue of IpaC identified thus far is Salmonella invasion protein C (SipC/SspC), which is essential for enterocyte invasion by Salmonella typhimurium. To explore the biochemical and functional relatedness of IpaC and SipC, recombinant derivatives of both proteins were purified so that their in vitro biochemical properties could be compared. Both proteins were found to: (i) enhance the entry of wild-type S. flexneri and S. typhimurium into cultured cells; (ii) interact with phospholipid membranes; and (iii) oligomerize in solution; however, IpaC appeared to be more efficient in carrying out several of the biochemical properties examined. Overall, the data indicate that purified IpaC and SipC are biochemically similar, although not identical with respect to their in vitro activities. To extend these observations, complementation analyses were conducted using S. flexneri SF621 and S. typhimurium SB220, neither of which is capable of invading epithelial cells because of non-polar null mutations in ipaC and sipC respectively. Interestingly, both ipaC and sipC restored invasiveness to SB220 whereas only ipaC restored invasiveness to SF621, suggesting that SipC lacks an activity possessed by IpaC. This functional difference is not at the level of secretion because IpaC and SipC are both secreted by SF621 and it does not appear to be because of SipC dependency on this native chaperone as coexpression of sipC and sicA in SF621 still failed to restore detectable invasiveness. Taken together, the data suggest that IpaC and SipC differ in either their ability to be translocated into host cells or in their function as effectors of host cell invasion. Because IpaB shares significant sequence homology with the YopB translocator of Yersinia species, the ability for IpaC and SipC to associate with this protein was explored as a potential indicator of translocation function. Both proteins were found to bind to purified IpaB with an apparent dissociation constant in the nanomolar range, suggesting that they may differ with respect to effector function. Interestingly, whereas SB220 expressing sipC behaved like wild-type Salmonella, in that it remained within its membrane-bound vacuole following entry into host cells, SB220 expressing ipaC was found in the cytoplasm of host cells. This observation indicates that IpaC and SipC are responsible for a major difference in the invasion strategies of Shigella and Salmonella, that is, they escape into the host cell cytoplasm. The implications of the role of each protein's biochemistry relative to its in vivo function is discussed.
BACKGROUND: Current DOQI guidelines encourage placing arteriovenous (AV) fistulas in more hemodialysis patients. However, many new fistulas fail to mature sufficiently to be usable for hemodialysis. Preoperative vascular mapping to identify suitable vessels may improve vascular access outcomes. The present study prospectively evaluated the effect of routine preoperative vascular mapping on the type of vascular accesses placed and their outcomes. METHODS: During a 17-month period, preoperative sonographic evaluation of the upper extremity arteries and veins was obtained routinely. The surgeons used the information obtained to plan the vascular access procedure. The types of access placed, their initial adequacy for dialysis, and their long-term outcomes were compared to institutional historical controls placed on the basis of physical examination alone. RESULTS: The proportion of fistulas placed increased from 34% during the historical control period to 64% with preoperative vascular mapping (P < 0.001). When all fistulas were assessed, the initial adequacy rate for dialysis increased mildly from 46 to 54% (P = 0.34). For the subset of forearm fistulas, the initial adequacy increased substantially from 34 to 54% (P = 0.06); the greatest improvement occurred among women (from 7 to 36%, P = 0.06) and diabetic patients (from 21 to 50%, P = 0.055). In contrast, the initial adequacy rate of upper arm fistulas was not improved by preoperative vascular mapping (59 vs. 56%, P = 0.75). Primary access failure was higher for fistulas than grafts (46.4 vs. 20.6%, P = 0.001), but the subsequent long-term failure rate was higher for grafts than fistulas (P < 0.05). Moreover, grafts required a threefold higher intervention rate (1.67 vs. 0.57 per year, P < 0.001) to maintain their patency. The overall effect of this strategy was to double the proportion of patients dialyzing with a fistula in our population from 16 to 34% (P < 0.001). CONCLUSIONS: Routine preoperative vascular mapping results in a marked increase in placement of AV fistulas, as well as an improvement in the adequacy of forearm fistulas for dialysis. This approach resulted in a substantial increase in the proportion of patients dialyzing with a fistula in our patient population. Fistulas have a higher primary failure rate than grafts, but have a lower subsequent failure rate and require fewer procedures to maintain their long-term patency.
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A study was undertaken to identify the "Business Idea", as defined by van der Heijden (1996), in The Family Planning Association of WA Inc (FPWA) which is a Non-Government Organisation (NGO) in Perth, Western Australia. This organisation was chosen as, along with many other NGOs, it was undergoing major changes in its funding, role and required outcomes. A qualitative interpretivist single case study methodology employing grounded theory research principles and methods was used to study the Business Idea framework in this setting. Thirty-four members of FPWA's staff were interviewed and data was managed using NUD*IST4 and Decision Explorer data storage, data retrieval and graphical reproduction facilities. Results indicated that images of the Business Idea model within FPWA were largely consistent across all staff levels excepting members of the Board of Management. Changes within the organisation were impacting heavily on staff, who needed to be assisted over the transitional phase. Strong leadership and corporate direction were identified as essential if the FPWA was to balance the strongly held sense of social justice amongst its staff with a need for greater productivity efficiency and accountability across the organisation.
We describe the clinical and pathologic findings in a murine model of mucopolysaccharidosis VII (Sly disease) that arose spontaneously in the C3H/HeOuJ mouse strain. Affected gus(mps2J)/gus(mps2J) mice are deficient in beta-glucuronidase because of insertion of an intracisternal A particle element into intron 8 of the gus structural gene. This is the first model of a human lysosomal storage disease caused by an intracisternal A particle element insertion. Mice with the gus(mps2J)/gus(mps2J) genotype have < 1% of normal beta-glucuronidase activity and secondary elevations of other lysosomal enzymes. The phenotype includes shortened life-span, dysmorphic features, and skeletal dysplasia. Lysosomal storage of glycosaminoglycans is widespread and affects the brain, skeleton, eye, ear, heart valves, aorta, and the fixed tissue macrophage system. Thus the phenotypic and pathologic alterations in gus(mps2J)/gus(mps2J) mice are similar to those in patients with mucopolysaccharidosis VII. The finding of antibodies to beta-glucuronidase in some older gus(mps2J)/gus(mps2J) mice suggests the mice produce sufficient enzyme to elicit an immune response. The gus(mps2J)/gus(mps2J) model provides another well-defined genetic system for the study of the pathophysiology of mucopolysaccharidosis and for evaluation of experimental therapies for lysosomal storage diseases. The disease in gus(mps2J)/gus(mps2J) mice is less severe than that seen in the previously characterized B6.C-H2(bm1)/ByBir-gus(mps)/gus(mps) mouse model. Furthermore, unlike gus(mps)/gus(mps) mice, gus(mps2J)/gus(mps2J) mice are fertile and breed to produce litters, all of which are mucopolysaccharidosis VII pups. This feature makes them extremely useful for testing intrauterine therapies.
A comparison has been made between accelerator mass spectrometry (AMS) analysis and liquid scintillation counting (LSC) of plasma, urine and faecal samples containing 14C-labelled drugs. In an in vitro study in which human plasma was spiked (the term spiked is used in Section 2.6) with 14C-Fluconazole (14C-FL) over a concentration range of 0.1-2.5 dpm/ml, a correlation coefficient of 0.999 was determined for AMS analysis versus extrapolated LSC data. No significant day to day (or inter-day)variation was seen (P < 0.05 by ANOVA). Coefficients of variation for these analyses ranged from 2.68 to 6.50%. In vivo studies in which rats were given a high (11.5 microCi/kg) or low (18.1 nCi/kg) radioactive dose (to model an exposure of 0.9 microSievert to man) of 14C-Fluticasone propionate(14C-FP) showed that there was also a good correspondence between AMS and LSC data. A mass balance study in a single the faeces by 96 h; less than 1% of the administered dose was excreted in the urine. The limit of reliable measurement of drug related material, above background concentrations, by AMS analysis in this study was approximately 0.1 dpm/ml for plasma, 0.01 dpm/ml for urine without any sample extraction or concentration and 0.01 dpm/ml for faecal extracts. The data reported here demonstrate that AMS is an ultrasensitive and reliable method for analysing 14C-labelled drugs in human and animal body fluids.
Burns often happen unexpectedly and have the potential to cause death, lifelong disfigurement and dysfunction. A critical part of burn management is assessing the depth and extent of injury. Burns are now commonly classified as superficial, superficial partial thickness, deep partial thickness and full thickness. A systematic approach to burn care focuses on the six "Cs": clothing, cooling, cleaning, chemoprophylaxis, covering and comforting (i.e., pain relief). The American Burn Association has established criteria for determining which patients can be managed as outpatients and which require hospital admission or referral to a burn center. Follow-up care is important to assess patients for infection, healing and ability to provide proper wound care. Complications of burns include slow healing, scar formation and contracture. Early surgical referral can often help prevent or lessen scarring and contractures. Family physicians should be alert for psychologic problems related to long-term disability or disfigurement from burn injuries.
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AIMS: To describe our experience in transit care of the critically ill in Northland and to highlight the multidisciplinary co-operation which renders this an efficient model of transit care in suburban and rural areas. METHODS: Since its inception in 1988, Northland's wholly community owned rescue helicopter has played an integral part in transit Intensive Care in Northland. This aids in transportation of medical and nursing intensive care staff to outlying primary hospitals for patient stabilisation, subsequent transfer of the patient to the intensive care unit (ICU) in Whangarei and, occasionally, for transfer to specialised critical care services in Auckland. RESULTS: As of August 1999, over 3,900 helicopter missions have been accomplished. A doctor, vetting each request for Medevac, minimises over-triage, thus ensuring adequate levels of transit care and effective utilisation of expensive resources. More than 90% of non-obstetric adult patients were ventilated and the number of Medevac missions increased over the years. The Accident Compensation Corporation (ACC) funds 40% of all flights, another 40% of flights are funded by Northland Health and the Order of St John funds the remainder. CONCLUSIONS: With a widespread geography, efficient transit care of the critically ill is imperative to quality hospital care and ensures equity of access to the rural populace. The Whangarei system of transit intensive care is an ideal template for suburban and rural areas.
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OBJECTIVE: The present study sought to identify characteristics of child sexual abuse cases which differentiate cases referred for criminal prosecution ("criminal-action") from those not referred ("dropped") by investigators. METHOD: The study sample consisted of 1043 children who completed a forensic interview for sexual abuse that allegedly occurred at the hands of an adult between January 1, 1993 and December 31, 1996 in Bernalillo County of New Mexico. Data was systematically obtained from forensic interview files and offender records at the local prosecutor's office. RESULTS: Differences between criminal-action and dropped cases were found in relation to the children (age, sex and ethnicity), the alleged offenders (age, sex and relationship to child), and the case characteristics (disclosure and injury to the child). CONCLUSIONS: The present study provided insight into the characteristics of a previously ignored population (reported child sexual abuse cases that are not referred for prosecution). Recommendations are made to address the needs of these children and their families.
This paper examines the role of word frequency in the computation of subject-verb number agreement. Previous research in both production and comprehension has demonstrated that processing difficulties can arise in sentence structures containing a singular subject noun followed by a plural "distractor" noun, as in The key to the cabinets.... A whole sentence reading task was employed to determine whether the relative frequency with which the distractor noun appears in its singular or plural form would affect the degree of processing difficulty experienced by readers. Results suggest that the agreement process is, indeed, sensitive to this factor and this finding is compatible with activation-based accounts of the implementation of number agreement.
To develop a model of early human adult B lymphopoiesis, we cultured CD34+CD38+CD10+ pro-B cells in contact with AFT024 stroma in X-VIVO10 media with 5% serum. The cytokines FLT3L + SCF + IL7 + IGF1 were added at day 0, IL4 + IL5 + IL6 + IL10 and soluble CD40 ligand at day 14, and Staph. aureus Cowan particles on day 21. Greater than 25-fold expansion of CD34+CD38+CD10+ cells was seen at 2 weeks, the majority being CD34-CD19+ pre-B cells. Differentiation to immature IgM+ B cells was seen at 3 weeks and mature IgD+ B cells at 4 weeks, with secretion of IgM into the media. Immature and mature B cells could also be generated from culture of CD34+CD10+CD19- and CD34+CD10+CD19+ cells under similar conditions. In conclusion, we have demonstrated in vitro differentiation of early pro-B cells, and possibly common lymphoid progenitor cells, to mature B cells. Additional stimuli, provided by T helper cells or dendritic cells for example, may be required for the generation of IgG+ B cells or plasma cells. However, our culture system should be a valuable tool to further investigate B cell biology and B cell malignancies such as multiple myeloma and lymphoma.
There have been a number of studies investigating metal uptake in plants on contaminated landfill sites, but little on their role as biomarkers to identify metal mobility for continuous monitoring purposes. Vegetation can be used as a biomonitor of site pollution, by identifying the mobilisation of heavy metals and by providing an understanding of their bioavailability. Plants selected were the common nettle (Uritica Dioica), bramble (Rubus Fruticosa) and sycamore (Acer Pseudoplatanus). A study of the soil fractionation was made to investigate the soil properties that are likely to influence metal mobility and a correlation exercise was undertaken to investigate if variations in concentration of metals in vegetation can reflect variations in concentration of the metals in soil. The soil was digested using aqua regia in a microwave closed vessel. The vegetation was digested using both microwave and a hydrogen peroxide-nitric acid mixture, refluxed on a heating block and a comparison made. The certified reference materials (CRMs) used were Standard Reference Material (SRM) 1547, peach leaves for vegetation (NIST) and for soil CRM 143R, sewage sludge-amended soil (BCR). The relative standard deviations (RSDs) were 2-6% for the analyses. Our findings show evidence of phytoextraction by some plants, (especially bramble and nettle), with certain plants, (sycamore) exhibiting signs of phytostabilisation. The evidence suggests that there is a degree of selectivity in metal uptake and partitioning within the plant compartments. It was also possible to correlate mobility phases of certain metals (Pb, Cu and Zn) using the soil and plant record. Zn and Cu exhibited the greatest potential to migrate from the roots to the leaves, with Pb found principally in the roots of ground vegetation. Our results suggest that analysis of bramble leaves, nettle leaves and roots can be used to monitor the mobility of Pb in the soil with nettle, bramble and sycamore leaves to monitor Cu and Zn.
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Staphylococcal superantigens have been implicated in the pathogenesis of atopic dermatitis (AD). This may occur through superantigenic activation of T lymphocytes and their subsequent induction of the skin homing receptor CLA on activated cells. We investigated the proliferative responses of peripheral blood mononuclear cells (PBMC) from 10 patients with an infective exacerbation of AD and six normal controls to the staphylococcal superantigens, staphylococcal enterotoxin A and B (SEA, SEB) and toxic shock syndrome toxin-1 (TSST-1), and the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A). We also assessed CLA and T cell receptor (TCR) Vbeta-chain expression by immunofluorescence and flow cytometry before and after stimulation. PBMC from AD patients showed two-fold increased proliferation to SEA and SEB (P < 0.01) compared with normals, whereas the response to mitogenic stimulation was identical. Analysis of (TCR) Vbeta-chain expression demonstrated increased use of superantigen-reactive Vbeta families in freshly isolated PBMC in AD patients compared with controls. This pattern of Vbeta-chain expression was only observed in the CLA+ but not the total population of T cells. Furthermore, there was a positive correlation between the enhanced PBMC proliferative response and increased expression of superantigen-reactive Vbeta families in atopic patients. These data support the concept that superantigens are important in the pathogenesis of this common condition, and also provide evidence that the increased use of certain Vbeta families in circulating, CLA+, skin homing lymphocytes is of functional significance.