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81.
Progress in the care of the critically ill patient with life-threatening infection has been hampered by inconsistent, often confusing terminology. The clinical syndrome of sepsis-familiar to all yet definable by none-describes a highly heterogeneous group of disorders with different causes and differing prognoses. The imminent availability of mediator-directed therapy has created a sense of urgency to develop better methods for delineating discrete clinical syndromes and to modulate the host response, which may bring both benefit and harm, depending on the clinical circumstances. The term systemic inflammatory response syndrome (SIRS) was introduced several years ago to describe the familiar clinical syndrome of sepsis, independent of its cause. SIRS can result from trauma, pancreatitis, drug reactions, autoimmune disease, and a host of other disorders; when it arises in response to infection, sepsis is said to be present. SIRS describes a dynamic process that has adaptive survival value for the host. The maladaptive consequence of this process in the critically ill patient is the development of progressive but potentially reversible remote organ dysfunction-the multiple organ dysfunction syndrome. The development of cogent conceptual frameworks for classification of the septic response in critically ill patients is more than a question of linguistic pedantry. Optimal therapy presupposes identification of an homogeneous patient population with a characteristic disease process and a predictable response to an intervention. Although progress has been made in identifying such groups of critically ill patients, the disappointing results of clinical trials of agents that so clearly demonstrate efficacy in animal models indicates that considerable work remains.  相似文献   
82.
OBJECTIVE: To review data supporting the hypothesis that syndrome X plays a major role in the pathogenesis of coronary artery disease (CAD), and the effects of lifestyle factors and pharmacologic interventions on insulin, other metabolic parameters, and outcomes. DATA SOURCES: MEDLINE (January 1966-August 1997) and Current Contents database searches identified applicable English-language experimental trials, epidemiologic studies, reviews, and editorials. STUDY SELECTION AND DATA EXTRACTION: Studies that were included addressed the role of insulin resistance and hyperinsulinemia in the pathogenesis of CAD or the effects of lifestyle factors and pharmacologic interventions on metabolic parameters and outcomes. DATA SYNTHESIS: The main characteristics of syndrome X are hyperinsulinemia and insulin resistance. These result in secondary syndrome X features, including hyperglycemia, increased very-low-density lipoprotein concentrations, decreased high-density lipoprotein cholesterol, and hypertension. Insulin resistance is worsened by obesity, and insulin has been shown to contribute to the development of hypertension. Other studies demonstrate that smoking adversely affects glucose and insulin concentrations. Animal studies have linked hyperinsulinemia and atherogenesis. These animal data have been confirmed by several large prospective and population studies that have identified associations between hyperinsulinemia and CAD. CONCLUSIONS: Strong evidence links insulin resistance and hyperinsulinemia to CAD. Lifestyle modifications play an important role in decreasing cardiovascular risk, and clinicians should strongly encourage such changes. Clinicians must also carefully consider the effects of antihypertensive, antihyperglycemic, and antidyslipidemic agents on patients' metabolic profiles when choosing appropriate therapeutic regimens. However, outcome data on many potentially beneficial agents, including calcium antagonists, alpha 1-adrenergic antagonists, angiotensin-converting enzyme inhibitors, metformin, acarbose, and troglitazone, are not yet available.  相似文献   
83.
One hundred and twenty-six cases of cerebellopontine angle tumors with various histologies are presented. Results of 75 operated vestibular neurinomas, 22 meningiomas, and 16 tumors with other histologies are discussed. The method of irradiation and non-radical surgery may be an alternative for treatment.  相似文献   
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Phosphoribulokinase (PRK), unique to photosynthetic organisms, is regulated in higher plants by thioredoxin-mediated thiol-disulfide exchange in a light-dependent manner. Prior attempts to overexpress the higher plant PRK gene in Escherichia coli for structure-function studies have been hampered by sensitivity of the recombinant protein to proteolysis as well as toxic effects of the protein on the host. To overcome these impediments, we have spliced the spinach PRK coding sequence immediately downstream from the AOX1 (alcohol oxidase) promoter of Pichia pastoris, displacing the chromosomal AOX1 gene. The PRK gene is now expressed, in response to methanol, at 4-6% of total soluble protein, without significant in vivo degradation of the recombinant enzyme. This recombinant spinach PRK is purified to homogeneity by successive anion-exchange and dye-affinity chromatography and is shown to be electrophoretically and kinetically indistinguishable from the authentic spinach counterpart. Site-specific replacement of all of PRK's cysteinyl residues (both individually and in combination) demonstrates a modest catalytically facilitative role for Cys-55 (one of the regulatory residues) and the lack of any catalytic role for Cys-16 (the other regulatory residue), Cys-244, or Cys-250. Mutants with seryl substitutions at position 55 display non-hyperbolic kinetics relative to the concentration of ribulose 5-phosphate. Sulfate restores hyperbolic kinetics and enhances kinase activity, presumably reflecting conformational differences between the position 55 mutants and wild-type enzyme. Catalytic competence of the C16S-C55S double mutant proves that mere loss of free sulfhydryl groups by oxidative regulation cannot account entirely for the accompanying total inactivation.  相似文献   
87.
An isocratic reversed-phase high-performance liquid chromatographic method with ultraviolet detection at 230 nm has been developed for the determination of paclitaxel in human plasma. Plasma samples were prepared by a selective one-step liquid-liquid extraction involving a mixture of acetonitrile-n-butyl chloride (1:4, v/v). Paclitaxel and the internal standard docetaxel were separated using a column packed with ODS-80A material, and a mobile phase consisting of water-methanol-tetrahydrofuran-ammonium hydroxide (37.5:60:2.5:0.1, v/v). The calibration graph for paclitaxel was linear in the range 10-500 ng/ml, with a lower limit of quantitation of 10 ng/ml, using 1 ml plasma samples. The extraction recoveries of spiked paclitaxel and docetaxel to drug-free human plasma were 89.6+/-8.52 and 93.7+/-5.0%, respectively. Validation data showed that the assay for paclitaxel is sensitive, selective, accurate and reproducible. The assay has been used in a single pharmacokinetic experiment in a patient to investigate the applicability of the method in vivo.  相似文献   
88.
BACKGROUND: Significant changes are restructurng the U.S. health care delivery system. National health reform is now extending itself into the public sector. Increased health and medical costs by federal and state governments are forcing a reevaluation of major entitlement programs, especially Medicaid. METHODS/RESULTS: Because Medicaid is the single largest item in many state budgets, states are now enrolling Medicaid patients into managed and coordinated care arrangements as a means to control costs and increase access to care. HMOs are not only competing for private patients but also actively seeking the Medicaid population. Nationally, almost one-fourth of all Medicaid patients are now enrolled in managed care plans. Various models and approaches have been developed by individual states. CONCLUSIONS: Because managed care enrollment in the Medicaid program has increased substantially in recent years, selected services including vision care are no longer rendered by any practitioner willing to accept Medicaid fees. Freedom of choice is now restricted to pre-selected and panel practitioners participating with the managed care program. The rules, regulations, billing procedures, fees, and program requisites will differ under managed care programs. Private optometric practitioners must consider entering economic and organizational relationships and linkages that make them attractive to managed care organizations.  相似文献   
89.
The polycistronic expression mechanism of the plant pararetrovirus figwort mosaic caulimovirus (FMV) depends upon cis-acting elements present in its pregenomic RNA and a trans-acting protein (P6) which is expressed from a monocistronic subgenomic RNA. Using transient expression of FMV-derived polycistronic reporter constructs in Nicotiana edwardsonii cell suspension protoplasts, we further analyzed the cis-acting elements involved in polycistronic expression. A cis-acting element located within the first 74 nucleotides of the 7,954-nucleotide pregenomic RNA appears to be essential for P6 to transactivate expression of an internal cistron. Expression of this internal cistron, in the presence of P6, is greatly enhanced by the combined presence of two cis-acting elements located at the 3' end of the polycistronic RNA. Surprisingly, deletion of the most upstream of these two 3' cis-acting elements exposed a negative-acting element located internally on the polycistronic RNA, at the 3' end of open reading frame I. The action of both this negative-acting internal element and the positive-acting 3' elements is more pronounced when the large 5' untranslated leader region is present. This indicates that the 5' untranslated leader region is central to regulation of the FMV gene expression mechanism. Although a limited set of elements suffices to direct polycistronic expression in this eukaryotic system, a complex interplay between elements is involved in the spatial regulation of the genes present on the pregenomic RNA of FMV.  相似文献   
90.
BACKGROUND: Insight into referral patterns provides general practitioners (GPs) and specialists with a frame of reference for their own work and enables assessment of the need for secondary care. Only approximate information is available. AIM: To determine how often, to which specialties and for what conditions children in different age groups are referred, as well as how often a condition is referred given the incidence in general practice. METHOD: From data of the Dutch National Survey of Morbidity and Interventions in General Practice, 63,753 new referrals (acute and non-acute) were analysed for children (0-14 years) from 103 participating practices (161 GPs) who registered. Practices were divided into four groups. Each group of practices participated for three consecutive months covering a whole year altogether. We calculated referral rates per 1000 children per year and referability rates per 100 episodes, which quantifies the a priori chance of a condition being referred for specialist care. RESULTS: The referral rate varied by age from 231 for children under 1 year old to 119 for those aged 10-14 years (mean 159). The specialties mainly involved were ENT, paediatrics, surgery, ophthalmology, dermatology and orthopaedics. Referrals in the first year of life were most frequently to paediatricians (123); among older children the referral rate to paediatricians decreased (mean 36). Referrals to ENT specialists were seen particularly in the age groups 1-4 (71) and 5-9 (53). For surgery, the referral rate increased by age from 19 to 34. Differences between boys and girls were small, except for surgery. The highest referral rates were for problems in the International Classification of Primary Care (ICPC) chapters: respiratory (28); musculoskeletal (25); ear (24) and eye (21). Referability rates were, in general, low for conditions referred to paediatrics and dermatology and high for surgery and ophthalmology. The variation in problems presented to each specialty is indicated by the proportion of all referrals constituted by the 10 most frequently referred diagnoses: from 35% for paediatrics to 81% for ENT; for ophthalmology, five diagnoses accounted for 83% of all referrals. CONCLUSIONS: The need for specialist care in childhood is clarified with detailed information for different age categories, specialties involved and variation in morbidity presented to specialists, as well as the proneness of conditions to be referred.  相似文献   
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