制度供给视角下的基本医疗体制改革之决策

基本医疗改革的财政投入模式应从单一关注医疗服务供给转向协同关注医疗服务产出，无过错医疗损害救济应纳入国家财政投入的预算体系。面对医疗损害的高发性，以救济为心的医疗侵权责任制度应向以预防中心的制度进行改革。医疗过失诉讼制度对医疗体系有着深刻的负面制约作用。基本医疗改革的决策应从更宏观的视角进行制度供给设计。     

Biological monitoring of environmental pollution and human exposure to some trace elements

The extent of environmental pollution and resulting human exposure to hazardous toxic chemicals in the environment is often difficult to assess. One of the possible alternative approaches to this problem is the use of the biological indicators to demonstrate environmental pollution. This approach appears to be particularly suitable for demonstrating exposure to potentially toxic trace elements. In addition to analyses of plant and animal specimens the element content of human hair as an indicator of exposures to arsenic, mercury, cadmium, lead, antimony, manganese, nickel and cobalt has been repeatedly confirmed as reliable, provided the analyses were carried out and evaluated on group diagnostic basis and were done in groups of individuals occupationally not exposed to these metals. Preferably groups of 10-year-old children are to be used when only environmental pollution is to be taken into account. Hair samples are incomparably easier to collect, transport and store than the alternative biological material such as blood and urine used commonly to demonstrate exposure to various toxic agents. Biological monitoring of environmental pollution cannot replace the standard procedures of measuring air, water and soil pollution; however, the technique appears to have the potential of being an effective tool search for the extent of environmental pollution and for delimitation of territorial boundaries of areas affected most by hazardous emissions containing potentially toxic trace elements.     

Hazards from chemicals: scientific questions and conflicts of interest.

All substances are toxic when the dose is large enough. In order to regulate the use of chemicals, we need to measure the level at which toxic effects are found. Epidemiological evidence suggests that present levels of chemical use do not lead to widespread harmful contamination of the human environment. For chemicals, most of the problems of toxicity are found in the workplace, while the population at large gets most of its toxic effects from voluntary exposure to substances such as tobacco smoke and ethanol. The prevention and control of toxic effects depends on a series of steps. This begins with measurement of toxicity in model systems, such as laboratory animals, and the estimation of the likely exposure of workers or consumers. Reliable extrapolation of information gathered from animals to the diverse and biochemically differing human population depends on understanding mechanisms of toxic effects. The toxic effect and mechanisms of action of substances such as carbon tetrachloride or paracetamol have been extensively investigated, and our ability to predict toxicity or develop antidotes to poisoning has had some success, but epidemiology is still an essential part of assessment of toxic effects of new chemicals. The example of phenobarbitone shows how animal experiments may well lead to conclusions which do not apply to man. After measurement of toxicity and assessment of likely hazards in use comes the final evaluation of the use of a chemical. This depends not only on its toxicity, but also on its usefulness. The direct effects on health may be small in comparison with the indirect advantageous effects which a useful substance such as vinyl chloride may bring. The assessment of risks and benefits of new chemicals can be partly removed from a political style of discourse, but the evaluation of the relative weight to be attached to these risks and benefits is inescapably political. The scientific contribution must be to allow the debate to take place in the light of maximum clarity of information about the consequences of use of chemicals.     

Safety of pyrethroid-treated mosquito nets

The use of insecticide treated nets (ITNs) for personal protection against malaria vector Anopheles mosquitoes (Diptera: Culicidae) has become popular during the past decade. With the precautions outlined in this paper, field use of pyrethroids--at concentrations recommended for treatment of mosquito nets--poses little or no hazard to people treating the nets or to users of the treated nets. With frequent exposure to low concentrations of pyrethroids, the risk of toxicity of any kind is remote. Pyrethroids entering the systemic circulation are rapidly metabolized to much less toxic metabolites. Toxicologically, pyrethroids have a useful characteristic--the production of skin paraesthesia--which gives an early indication of exposure. This reversible symptom of exposure is due to transient stimulation of peripheral sensory nerves and not a toxic effect. In the retail market, for home use, the provision of proper packaging and labelling, with clear instructions on safe and effective use of the product are most important. Because many domestic users of pyrethroid 'home treatment kits' for ITNs may not be fully literate, it is essential that 'instructions for use' should be portrayed via pictograms with supporting text in appropriate local language(s).     

Record linkage and the identification of long-term environmental hazards.

The long-term effects of toxic substances in man that have been discovered so far have involved gross relative risks or bizarre effects, or have stumbled upon by chance or because of special circumstances. These facts and some recent epidemiological evidence together suggest that a systematic approach with better methods would reveal the effects of many more toxic substances, particularly in manufacturing industry. Record linkage is a powerful tool because it makes possible the correlation of indicators of exposure with indicators of the biological effect of such exposure in the same persons or in their progeny even after considerable periods of time have elapsed. A system of linked records exists in England and Wales which is at present used by research workers to follow up samples of persons defined in various ways, e.g. in respect of exposure to a suspected toxic factor. In this way hypotheses about substances causing cancer or other lethal effects can be tested. It is suggested that there are two additional ways in which record linkage techniques could be used to identify substances with long-term toxic effects: the first would be by setting up a register of women employed in industry during pregnancy and linking this register to records of the occurrence of congenital malformations and of stillbirth or death in their children; the second would be to follow samples of workers in manufacturing industry, notably those engaged in the manufacture of products from raw materials including the chemical industry, to death and to the development of cancer. Regular analyses of material from these two systems of linked records would provide the basis for a monitoring system for certain gross effects of long-term toxic substances in man. There are two principal obstacles to further progress in this field. The first is the lack of a clear statement of public policy concerning the issues of confidentiality and informed consent in the use of identifiable personal records for medical research. A settlement is needed which defines the proper limits of their use in the interests of health with safeguards to privacy. The second obstacle is a lack of resources to improve the quality, accessibility and organization of the appropriate data.     

Pheo or not a pheo,that is the question.

The current fault-based tort system assumes that claims made against physicians are inversely related to the quality of care they provide. In this study we identified physician characteristics associated with elements of medical care that make physicians vulnerable to malpractice claims. A sample of physicians (n = 248) thought to be at high or low risk for claims was surveyed on various personal and professional characteristics. Statistical analysis showed that 9 characteristics predicted risk group. High risk was associated with increased age, surgical specialty, emergency department coverage, increased days away from practice, and the feeling that the litigation climate was "unfair." Low risk was associated with scheduling enough time to talk with patients, answering patients'' telephone calls directly, feeling "satisfied" with practice arrangements, and acknowledging greater emotional distress. Prediction was more accurate for physicians in practice 15 years or less. We conclude that a relationship exists between a history of malpractice claims and selected physician characteristics.     

The Role of Soil Microbial Tests in Ecological Risk Assessment: Differentiating between Exposure and Effects

The use of soil microorganisms in ecological risk assessment is hampered by an unclear dose-response relationship for most contaminants. Establishing dose-response curves for soil microbial communities requires that one have a clear estimate of exposure at the site of toxic action and a response free of confounding environmental factors. It is not clear what methods can estimate toxicant dose at the site of toxic action or determine microbial response to a toxicant. Pollution-induced community tolerance (PICT) is one possible estimate of microbial toxicant exposure. The PICT hypothesis is that the tolerance of a microbial community is proportional to the in situ dose. This method automatically corrects for differences due to differences in soil physical-chemical variables between samples. Various components of the soil nitrogen cycle can act as microbial bioindicators of toxicant impacts. Estimating denitrifica-tion activity presents a number of advantages over other components of the nitrogen cycle. Denitrifying bacteria come from a diversity of habitats, can be autotrophic or heterotrophic, and denitrification is a well-defined enzymatic system, which allows the use of molecular tools. Determining denitrification may be a good estimate of effects of toxicants on microbial communities. However, given the state of our ignorance regarding soil microbial community structure and function, redundant estimates of exposure and effect are necessary to adequately characterize the response of microbial communities to toxicants.     

A prototype microfluidic chip using fluorescent yeast for detection of toxic compounds

A microfluidic chip has been developed to enable the screening of chemicals for environmental toxicity. The microfluidic approach offers several advantages over macro-scale systems for toxicity screening, including low cost and flexibility in design. This design flexibility means the chips can be produced with multiple channels or chambers which can be used to screen for different toxic compounds, or the same toxicant at different concentrations. Saccharomyces cerevisiae containing fluorescent markers are ideal candidates for the microfluidic screening system as fluorescence is emitted without the need of additional reagents. Microfluidic chips containing eight multi-parallel channels have been developed to retain yeast within the chip and allow exposure of them to toxic compounds. The recombinant yeast used was GreenScreentrade mark which expresses green fluorescent proteins when is exposed to genotoxins. After exposure of the yeast to target compounds, the fluorescence emission was detected using an inverted microscope. Qualitative and quantitative comparisons of the fluorescent emission were performed. Results indicated that fluorescent intensity per area significantly increases upon exposure to methyl-methanesulfonate, a well known genotoxic compound. The microfluidic approach reported here is an excellent tool for cell-based screening and detection of different toxicities. The device has the potential for use by industrial manufacturers to detect and reduce the production and discharge of toxic compounds, as well as to characterise already polluted environments.     

Contingent Fees in Medical Malpractice Litigation—A Qualitative Assessment

The medical profession has experienced high liability insurance premiums accompanied by widespread use of contingent fees in medical malpractice litigation. It is worthwhile, therefore, to assess qualitatively the merits of contingent fees, the evidence suggesting that they are associated with unjustified litigation and their implications for the medical and legal professions.     

Tobacco and pregnancy: overview of exposures and effects

This opening article will review the epidemiology of the effects of cigarette smoking and other forms of tobacco exposure on human development. Sources of exposure described include cigarettes and other forms of smoked tobacco, secondhand (environmental) tobacco smoke, several forms of smokeless tobacco, and nicotine from nicotine replacement therapy. Exposure is immense and worldwide, most of it due to smoking, but in some parts of the world and in some populations, smoking is exceeded by smokeless tobacco use. Nicotine and carbon monoxide exposure are of large concern, but cigarette smoke contains over 4000 chemical constituents and additives including known carcinogens, toxic heavy metals, and many chemicals untested for developmental toxicity. The impact of tobacco on human development will be reviewed. Fertility, conception, survival of the conceptus, most phases and aspects of development studied to date, as well as postnatal survival and health are adversely impacted by maternal tobacco use or exposure. Effects in surviving offspring are probably life-long, and are still being elucidated. It is hoped that this review and those to follow in this issue will serve to keep a focus on the critical and continuing problem of tobacco use impacting human development.     

Radiation litigation in retrospect

Most of the radiation litigation filed against the United States pursuant to the Federal Tort Claims Act has been defended by asserting federal sovereign immunity or by proving that the plaintiff's injury is unrelated to his radiation exposure. This paper reports that the second defense is best advanced by comprehensive pretrial investigation of the plaintiff's claim, which frequently results in voluntary dismissal of the legal action.     

The effect of additive compounds on glycerol-induced damage to human chondrocytes

High concentrations of cryoprotective agents are required for cryopreservation techniques such as vitrification. Glycerol is a common cryoprotective agent used in cryopreservation protocols but this agent is toxic at high concentrations. This work is an attempt to mitigate the toxic effects of high concentrations of glycerol on intact chondrocytes in human knee articular cartilage from total knee arthroplasty patients by simultaneous exposure to glycerol and a variety of additive compounds. The resulting cell viability in the cartilage samples as measured by membrane integrity staining showed that, in at least one concentration or in combination, all of the tested additive compounds (tetramethylpyrazine, ascorbic acid, chondroitin sulphate, glucosamine sulphate) were able to reduce the deleterious effects of glycerol exposure when examination of membrane integrity took place on a delayed time frame. The use of additive compounds to reduce cryoprotectant toxicity in articular cartilage may help improve cell recovery after cryopreservation.     

Stearylamine permeabilizes the lysosomal membrane to cystine and sialic acid

Cystine efflux from isolated rat liver lysosomes was enhanced by concentrations of stearylamine that were above the critical micellar concentration. Lysosomal latency, pH, and activity of the proton-translocating ATPase were largely unaffected under controlled experimental conditions. Loss of lysosomal latency was observed at higher stearylamine to protein ratios consistent with a detergent-like mechanism of action. Partially purified cultured fibroblast lysosomes with either defective cystine or sialic acid transport lost their stored material upon exposure to stearylamine. Concentrations of stearylamine which were effective for lysosomal efflux were highly toxic for cultured fibroblasts, thus limiting its use. Under specific conditions, stearylamine apparently selectively permeabilizes the lysosomal membrane. A similar acting, but less toxic agent may be of use in the treatment of lysosomal transport disorders.     

Preconditioning of human smooth muscle cells via cyclopentenone prostaglandins protects against toxic effects of oxidized low-density lipoprotein

Human vascular smooth muscle cells (SMC) exhibit upregulation of inducible heat shock protein 70 (Hsp70), upon exposure to oxidized low-density lipoproteins (LDL(ox)). The presence of Hsp70 is thought to protect the cell against the toxic effects of the modified lipoprotein. In order to test this hypothesis, Hsp70 in SMC was upregulated by exposure to Delta(12) prostaglandin J(2) (Delta(12)PGJ(2)) before cells were exposed to LDL(ox). Hsp70 levels were measured after exposure to Delta(12)PGJ(2) and before exposure to LDL(ox). Cell protection was monitored after LDL(ox) exposure by determination of cell toxicity measured by cell lactate dehydrogenase (LDH) release into the medium. Cells treated with Delta(12)PGJ(2) exhibited a 23-fold increase in Hsp70 levels and 56% lower LDH activity release after exposure to LDL(ox) when compared to cells that were not pretreated with Delta(12)PGJ(2). In addition, cells pretreated with prostaglandins that did not induce Hsp70 did not exhibit increased tolerance against the toxic effects of LDL(ox). The results support a protective role for Hsp70 against the toxic effects of LDL(ox) and hint at the potential for the use of small molecules for the prevention of deleterious effects of LDL(ox) through heat shock protein upregulation.     

Lethal and sublethal toxicity of fipronil and imidacloprid on Psyttalia concolor (Hymenoptera: Braconidae)

Psyttalia concolor (Szèpligeti) (Hymenoptera: Braconidae) is a koinobiont endoparasitoid of several species of tephritid (Diptera) larvae, such as Bactrocera oleae (Gmelin) and Ceratitis capitata (Wiedemann). Here, we report on the effects of imidacloprid and fipronil on P. concolor females, when different routes of exposure were evaluated: residual contact (cover and bait sprays) and via treatment of host species. Moreover, the persistence of the bait formulated compound also was studied. For each experiment, lethal (mortality) and sublethal effects (parasitization rate or longevity) were studied. Fipronil produced 100% mortality irrespective of exposure route, and it was very persistent, because 34-d-old residues still produced this high mortality rate, being as toxic or even more toxic than the reference product dimethoate. Toxicity of imidacloprid depends on the mode of exposure, although always remained less toxic than dimethoate. Imidacloprid caused high mortality or sublethal effect to the progeny in cover sprays and when applied via treated host, being harmless in bait sprays application. In conclusion, our results suggest that fipronil should not be used in the field when the parasitoid is present. On the contrary, although imidacloprid is physiologically active against females of P. concolor, ecological selectivity may result through the use of bait treatment.     

Approaches for the development of occupational exposure limits for man-made mineral fibres (MMMFs)

Occupational exposure limits (OELs) are an essential tool in the control of exposure to hazardous chemical agents, and serve to minimise the occurrence of occupational diseases associated with such exposure. The setting of OELs, together with other associated measures, forms an essential part of the European Community's strategy on health and safety at work, upon which the legislative framework for the protection of workers from risks related to chemical agents is based. The European Commission is assisted by the Scientific Committee on Occupational Exposure Limits (SCOEL) in its work of setting OELs for hazardous chemical agents. The procedure for setting OELs requires information on the toxic mechanisms of an agent that should allow to differentiate between thresholded and non-thresholded mechanisms. In the first case, a no-observed adverse effect level (NOAEL) can be defined, which can be the basis for a derivation of an OEL. In the latter case, any exposure is correlated with a certain risk. If adequate scientific data are available, SCOEL estimates the risk associated with a series of exposure levels. This can then be used for guidance, when setting OELs at European level. Man-made mineral fibres (MMMFs) are widely used at different worksites. MMMF products can release airborne respirable fibres during their production, use and removal. According to the classification of the EU system, all MMMF fibres are considered to be irritants and are classified for carcinogenicity. EU legislation foresees the use of limit values as one of the provisions for the protection of workers from the risks related to exposure to carcinogens. In the following paper, the research requirements identified by SCOEL for the development of OELs for MMMFs will be presented.     

Rapid antibody screening by membrane chromatographic immunoassay technique

This paper describes a novel membrane chromatographic immunoassay technique suitable for rapid screening of antibodies in serum samples. This technique could potentially be utilized for antibody screening in situations where screening for exposure to one of several possible antigens is required. A synthetic microporous membrane is first selectively loaded with antibodies from the test serum sample by hydrophobic interaction. The in situ affinity membrane thus formed is sequentially pulsed with the antigens corresponding to the antibodies being screened. From the antigen chromatogram peak profile thus obtained, inferences about the antibodies present in the serum sample can then easily be made. This technique in addition to being rapid and direct is conceptually simple, and does not use any expensive media or reagents. It would potentially be useful for rapid diagnosis of infections as well as for rapid assessment of conditions such as envenomation or exposure to toxic substances.     

The challenges of litigation in US courts and the actions tissue banks can take to meet those challenges

The growth of tissue banking from local non-profit organizations to national and multi-national corporations has increased the likelihood of litigation against tissue banks. The acquisition of tissue banks by corporate entities, many of whom are based in the US, means that tissue banks need to be prepared for the challenge of litigation in the US courts. The purpose of this paper is to help tissue banks meet those challenges by describing the nature of US litigation, the most common types of lawsuits against tissue banks and the steps that tissue banks can take to prepare for litigation in the US.     

How do herbivorous insects cope with noxious secondary plant compounds in their diet?

Herbivorous insects use a variety of physiological mechanisms to cope with noxious (i.e., unpalatable and/or toxic) compounds in their food plants. Here, I review what is known about this coping process, focusing on one species of caterpillar, the tobacco hornworm (Manduca sexta). Herbivorous insects possess both preingestive (i.e., chemosensory) and postingestive response mechanisms for detecting plant secondary compounds. Stimulation of either class of detection mechanism inhibits feeding rapidly by reducing biting rate and/or bite size. This aversive response is highly adaptive during encounters with secondary plant compounds that are toxic. The insect's dilemma is that many harmless or mildly toxic compounds also activate the aversive response. To overcome this dilemma, herbivorous insects employ at least three mechanisms for selectively deactivating their aversive response to relatively harmless secondary plant compounds: (1) the presence of carbohydrates can mask the unpalatable taste of some secondary plant compounds; (2) prolonged dietary exposure to some unpalatable secondary plant compounds can initiate long-term adaptation mechanisms in the peripheral and central gustatory system; and (3) dietary exposure to toxic compounds can induce production of P450 detoxication enzymes. Thus, herbivorous insects utilize an integrated suite of physiological mechanisms to detect potentially toxic compounds in foods, and then selectively adapt to those that do not pose a serious threat to their growth and survivorship.     

DEBtox theory and matrix population models as helpful tools in understanding the interaction between toxic cyanobacteria and zooplankton

Bioassays were performed to find out how field samples of the toxic cyanobacteria Microcystis aeruginosa affect Moina micrura, a cladoceran found in the tropical Jacarepagua Lagoon (Rio de Janeiro, Brazil). The DEBtox (Dynamic Energy Budget theory applied to toxicity data) approach has been proposed for use in analysing chronic toxicity tests as an alternative to calculating the usual safety parameters (NOEC, ECx). DEBtox theory deals with the energy balance between physiological processes (assimilation, maintenance, growth and reproduction), and it can be used to investigate and compare various hypotheses concerning the mechanism of action of a toxicant. Even though the DEBtox framework was designed for standard toxicity bioassays carried out with standard species (fish, daphnids), we applied the growth and reproduction models to M. micrura, by adapting the data available using a weight-length allometric relationship. Our modelling approach appeared to be very relevant at the individual level, and confirmed previous conclusions about the toxic mechanism. In our study we also wanted to assess the toxic effects at the population level, which is a more relevant endpoint in risk assessment. We therefore incorporated both lethal and sublethal toxic effects in a matrix population model used to calculate the finite rate of population change as a continuous function of the exposure concentration. Alongside this calculation, we constructed a confidence band to predict the critical exposure concentration for population health. Finally, we discuss our findings with regard to the prospects for further refining the analysis of ecotoxicological data.