The record of pesticide regulation in the United Kingdom appears to be good. Close examination, however, now reveals a number of shortcomings in past pesticide regulatory policy. Pesticides cleared for use in 1960 have been withdrawn over the last 30 years because of evidence on animal carcinogenicity not available at that time. Government, public and scientific attitudes to pesticide hazards today are briefly analysed. Several deficiencies and limitations in current pesticide clearance practice are outlined and an alternative approach is described. 相似文献
Background. Heparin bonding of the cardiopulmonary bypass (CPB) circuit may be associated with a reduced inflammatory response and improved clinical outcome. The relative contribution of a heparin-bonded oxygenator (ie, >80% of circuit surface area) to these effects was assessed in a group of pediatric patients.
Methods. Twenty-one pediatric patients undergoing CPB operations were assigned randomly to receive either a heparin-bonded oxygenator (group H, n = 11) or a nonbonded oxygenator (group C, n = 10) in otherwise nonbonded circuits. The two groups were similar in pathology, age, weight, CPB time, and cross-clamp time. Plasma levels of the cytokines tumor necrosis factor-, interleukin-6, and interleukin-8, as well as terminal complement complex, neutrophils, and elastase, were analyzed before, during, and after CPB.
Results. Significant levels of tumor necrosis factor- were not detected in either group. Plasma levels of all other markers increased during and after CPB compared with baseline. Plasma levels of interleukin-6 peaked in both groups 2 hours after the administration of protamine but remained significantly higher in group C 24 hours after operation. Plasma concentrations of interleukin-8 peaked at similar levels in both groups 30 minutes after protamine administration and returned to baseline thereafter. Levels of terminal complement complex and elastase peaked in both groups 30 minutes after protamine administration. Plasma levels of terminal complement complex were significantly higher at the end of CPB and after protamine administration in group C. Elastase levels were significantly higher 2 and 24 hours after CPB in group C. The ventilation time of patients in group H was significantly lower than that of patients in group C: 10 (range, 3 to 24) versus 22 (range, 7 to 24) hours, respectively (p < 0.01).
Conclusions. The present study confirms the proinflammatory nature of pediatric operations and demonstrates a lessened systemic inflammatory response with the use of heparin-bonded oxygenators. This is achieved without bonding of the entire circuit, which could have significant cost-benefit implications by negating the need for custom-built heparin-bonded circuitry. 相似文献
This review summarises recent advances made in microscopic techniques (fluorescence and peptide nucleic acids) and culture techniques (solid, liquid, radiometric, and non-radiometric systems) and in the development of rapid methods for the identification of mycobacterial cultures (high performance liquid chromatography, thin layer chromatography, RNA sequencing, and polymerase chain reaction restriction enzyme assays). The role of molecular amplification systems in identifying Mycobacterium tuberculosis is described. Most methods record high specificity and sensitivity for smear positive sputum but have variable sensitivity for sputum smear negative and extrapulmonary specimens. Specimen quality will affect the performance of these assays and organisational delays, such as the batching of specimens, can reduce the time saved. In house assays can be as effective as commercial systems as long as appropriate controls are used. 相似文献
High levels of serum cholesterol and disruptions of the blood brain barrier (BBB) have all been implicated as underlying mechanisms in the pathogenesis of Alzheimer's disease. Results from studies conducted in animals and humans suggest that caffeine might be protective against Alzheimer's disease but by poorly understood mechanisms. Using rabbits fed a cholesterol-enriched diet, we tested our hypothesis that chronic ingestion of caffeine protects against high cholesterol diet-induced disruptions of the BBB. New Zealand rabbits were fed a 2% cholesterol-enriched diet, and 3 mg caffeine was administered daily in drinking water for 12 weeks. Total cholesterol and caffeine concentrations from blood were measured. Olfactory bulbs (and for some studies hippocampus and cerebral cortex as well) were evaluated for BBB leakage, BBB tight junction protein expression levels, activation of astrocytes, and microglia density using histological, immunostaining and immunoblotting techniques. We found that caffeine blocked high cholesterol diet-induced increases in extravasation of IgG and fibrinogen, increases in leakage of Evan's blue dye, decreases in levels of the tight junction proteins occludin and ZO-1, increases in astrocytes activation and microglia density where IgG extravasation was present. Chronic ingestion of caffeine protects against high cholesterol diet-induced increases in disruptions of the BBB, and caffeine and drugs similar to caffeine might be useful in the treatment of Alzheimer's disease. 相似文献
Kinase-related protein (KRP) and caldesmon are abundant myosin-binding proteins of smooth muscle. KRP induces the assembly
of unphosphorylated smooth muscle myosin filaments in the presence of ATP by promoting the unfolded state of myosin. Based
upon electron microscopy data, it was suggested that caldesmon also possessed a KRP-like activity (Katayama et al., 1995, J Biol Chem 270: 3919–3925). However, the nature of its activity remains obscure since caldesmon does not affect the equilibrium between
the folded and unfolded state of myosin. Therefore, to gain some insight into this problem we compared the effects of KRP
and caldesmon, separately, and together on myosin filaments using turbidity measurements, protein sedimentation and electron
microscopy. Turbidity assays demonstrated that KRP reduced myosin filament aggregation, while caldesmon had no effect. Additionally,
neither caldesmon nor its N-terminal myosin binding domain (N152) induced myosin polymerization at subthreshold Mg2+ concentrations in the presence of ATP, whereas the filament promoting action of KRP was enhanced by Mg2+. Moreover, the amino-terminal myosin binding fragment of caldesmon, like the whole protein, antagonizes Mg2+-induced myosin filament formation. In electron microscopy experiments, caldesmon shortened myosin filaments in the presence
of Mg2+ and KRP, but N152 failed to change their appearance from control. Therefore, the primary distinction between caldesmon and
KRP appears to be that caldesmon interacts with myosin to limit filament extension, while KRP induces filament propagation
into defined polymers. Transfection of tagged-KRP into fibroblasts and overlay of fibroblast cytoskeletons with Cy3KRP demonstrated
that KRP colocalizes with myosin structures in vivo. We propose a new model that through their independent binding to myosin and differential effects on myosin dynamics, caldesmon
and KRP can, in concert, control the length and polymerization state of myosin filaments.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
Flow rate and pressure difference (or head) are key variables needed in the control of implantable rotary blood pumps. However, use of flow and/or pressure probes can decrease reliability and increase system power consumption and expense. For a given fluid viscosity, the flow state is determined by any 2 of the 4 pump variables: Flow, pressure difference, speed, and motor input power can be used. Thus, if viscosity is known or if its influence is sufficiently small, flow rate and pressure difference can be estimated from the motor speed and motor input power. For the VentrAssist centrifugal blood pump, which uses a hydrodynamic bearing, sensorless flow and pressure head estimation accuracy of 2 of our impeller designs were compared for a viscosity range of 1.2 to 4.5 mPas. This showed impeller design optimization can improve estimation accuracy. We also compared estimation accuracy using 2 blood analogues used in vitro, aqueous glycerol and red blood cells suspended in Haemaccel. The nature of the blood analogue and not only the viscosity of the fluid seems to influence estimation accuracy in our pump. 相似文献
PURPOSE: To ascertain parents' and physicians' assessments of quality of end-of-life care for children with cancer and to determine factors associated with high-quality care as perceived by parents and physicians. METHODS: A survey was conducted between 1997 and 2001 of 144 parents of children who received treatment at the Dana-Farber Cancer Institute and Children's Hospital (Boston, MA) or Children's Hospitals and Clinics of St Paul and Minneapolis, MN, between 1990 and 1999 (65% of those located and eligible) and 52 pediatric oncologists. RESULTS: In multivariable models, higher parent ratings of physician care were associated with physicians giving clear information about what to expect in the end-of-life period (odds ratio [OR] = 19.90, P = .02), communicating with care and sensitivity (OR = 7.67, P < .01), communicating directly with the child when appropriate (OR = 11.18, P < .01), and preparing the parent for circumstances surrounding the child's death (OR = 4.84, P = .03). Parent reports of the child's pain and suffering were not significant correlates of parental ratings of care (P = .93 and .35, respectively). Oncologists' ratings of care were inversely associated with the parent's report of the child's experience of pain (OR = 0.15, P = .01) and more than 10 hospital days in the last month of life (OR = 0.24, P < .01). Parent-rated communication factors were not correlates of oncologist-rated care. No association was found between parent and physician care ratings (P = .88). CONCLUSION: For parents of children who die of cancer, doctor-patient communication is the principal determinant of high-quality physician care. In contrast, physicians' care ratings depend on biomedical rather than relational aspects of care. 相似文献