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  • 1
    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract The paper presents a mathematical analysis of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. The analysis indicates that for such a therapy to be successful, it must protect the transduced cells against HIV-induced death. The transduced cells will not survive as a population if the gene therapy only blocks the spread of virus from transduced cells that become infected. The analysis also suggests that the degree of protection against disease-related cell death provided by the gene therapy is more important than the fraction of cells that is initially transduced. If only a small fraction of the cells can be transduced, transduction of T helper cells and transduction of haematopoietic progenitor cells will result in the same steady-state level of transduced T helper cells. For gene therapy to be efficient against HIV infection, our analysis suggests that a 100% protection against viral escape must be obtained. The study also suggests that a gene therapy against HIV infection should be designed to give the transduced cells a partial but not necessarily total protection against HIV-induced cell death, and to avoid the production of viral mutants insensitive to the gene therapy.
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  • 2
    ISSN: 1432-2013
    Keywords: Salivary secretion ; Potassium transport ; Sodium transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated cat submandibular glands were perfused with Locke solutions in a thermostated chamber. Passive loss of potassium and uptake of sodium was achieved either by increasing the permeability of the cell membranes by acetylcholine (ACh) or by inhibiting the sodium-potassium pump reversibly by cooling or by removal of extracellular potassium. Irrespective of the way by which the cells were potassium depleted and sodium loaded, re-establishment of normal conditions was sufficient to cause an active net uptake of potassium (probably coupled to net extrusion of sodium). However, while ACh-induced changes in intracellular concentrations of monovalent cations were accompanied by salivary secretion, virtually no secretion was observed when normal conditions were re-established after concentration changes caused by inhibiting the sodium-potassium pump. It is concluded that while the transport mechanisms responsible for the maintenance of the intracellular concentrations of monovalent cations undoubtedly is a (Na+−K+)-activated ATPase, the transport mechanism responsible for the formation of the primary saliva is probably of a different type, since it apparently is not directly activated by the intracellular sodium concentration.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of epidemiology 13 (1997), S. 387-393 
    ISSN: 1573-7284
    Keywords: Behaviour/knowledge/attitudes ; Disease-transmission-patient-to-personnel ; Needlestick-injuries ; Prevention-and-control ; Prevention/education ; Risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The objective of this study was to describe the mechanisms of percutaneous blood exposure (PCE) among doctors and discuss rational strategies for prevention. Data were obtained as part of a nation-wide questionnaire survey of occupational blood exposure among hospital employed doctors in Denmark. The doctors were asked to describe their most recent PCE, if any, within the previous 3 months. Detailed information on the instruments, procedures, circumstances and mechanisms that caused the PCE was obtained. Of 9375 doctors, 6256 (67%) responded, and 6005 questionnaires were eligible for analysis. Of 971 described PCE the majority were caused by suture needles (n = 483), IV-catheter-stylets (n = 94), injection needles (n = 75), phlebotomy needles (n = 53), scalpels (n = 45), arterial blood sample needles (n = 41) and bone fragments (n = 23). Inattentiveness was the most common cause, contributing to 30.5% of all PCE. Use of fingers rather than instruments was a major cause of injury in surgical specialties and was a contributing cause of 36.9% PCE on suture needles. Common contributing causes when fingers were used (n = 199) were poor space in (30.2%) or view of (18.6%) the operation field. It was often argued that instruments were not practical to use or might harm the tissue. Of 689 PCE in surgical specialties, 17.4% were inflicted by colleagues. Up to 53.3% of PCE on hollow-bore needles could be attributed to unsafe routines like recapping only, but other mechanisms like sudden patient movements and ‘acute situation’ were common, especially in the case of PCE on iv-catheter-stylets. It is concluded that the exposure mechanisms of PCE reflect both unsafe routines, difficult working conditions and unsafe devices. Education in safer working routines are needed in all specialties. Introduction of safer devices should have a high priority in surgical specialties, and should be considered in non-surgical specialties too.
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  • 4
    ISSN: 1573-7284
    Keywords: Disease-transmission ; Health-personnel ; Needlestick injuries ; Occupational exposure ; Risk factors ; Universal precautions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Occupational blood exposures involves a risk of transmission of serious infections. We performed a nation-wide survey, to describe the incidence and risk factors of percutaneous (PCE) and mucocutaneous (MCE) blood exposures among hospital employed doctors in Denmark. Of 9,374 questionnaires, 6,256 (67%) were returned and 6,005 were eligible for analysis. The highest risk per person-risk-year (pry) was found in General surgery, Neurosurgery, Obstetrics-Gynaecology and Orthopaedic surgery (6.2--8.5 PCE/pry and 7.3--8.8 MCE/pry). The second risk group was Anaesthesiology and Oto-rhino-laryngology (2.6--3.1 PCE/pry and 6.0--6.9 MCE/pry). Finally Pathology, Internal medicine, Radiology and Paediatrics had a considerable risk (0.8--1.3 PCE/pry and 1.3--2.9 MCE/pry). Potential risk factors were examined by Poisson regression. Employment as senior as compared to junior doctor was associated with a higher risk of PCE (RR 2.2) and MCE (RR up to 2.7 depending on experience) among surgeons and an increased risk of PCE in anaesthetists (RR 1.7). In contrast, senior physicians in Internal medicine, Radiology and Paediatrics had a several fold lower risk of PCE (RR 0.6) and MCE (RR 0.6 in males, 0.3 in females). Only 35% adhered to the basic principles of universal precautions (UP) and non-compliance was associated with a considerably increased risk of both MCE and PCE, especially in non-surgical specialties. In conclusion, we found an unacceptably high incidence of occupational blood exposures among Danish doctors. Non-compliance with UP was associated with an increased risk of exposure and efforts to improve compliance with UP as well as implementation and evaluation of other preventive measures are needed.
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  • 5
    ISSN: 1573-0689
    Keywords: Enhancement ; antibodies ; HIV ; mathematical model ; vaccine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract Antibodies (Ab) specific for epitopes on HIV glycoprotein gp120 or gp41 can inhibit or enhance HIV infection of human cellsin vitro. These effects may have significant implications both for the pathogenesis of chronic HIV infection and for vaccine development. A particularly puzzling findingin vitro is antibody dependent enhancement (ADE) at low concentrations of Ab while high concentrations of the same antibody inhibit infection. Similar phenomena have been observed for other enveloped viruses. Antibodies can inhibit infection by several mechanisms. However, by binding to receptors on target cells, virus bound antibodies can also enhance adhesion to these cells and thereby facilitate infection. We propose a mathematical model that describes how these two processes interact and hereby provide an explanation for the observed enhancement/neutralization phenomena. Simulation results were validated with good agreement against empirical data from antibody dependent enhancement of HIV infection of monocytoid (U937) cellsin vitro, and the model should be applicable to otherin vitro systems involving different cells and viruses. The model indicates that for the common type of HIV neutralizing antibody, acting at a post-CD4-binding step, there is a neutralizing ‘window’ defined by the affinity and concentration of antibody.
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