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PubMed2026

Research on the genome of microorganisms: ethical considerations and recommendations regarding the incidental bystander sequencing of human genetic material.

In genomic research primarily targeting microorganisms (or pathogens), a substantial risk exists that the presence of human genetic bycatch is not sufficiently recognised, and that the potential harm of unwarranted analysis, access, or sharing of human genetic bystander data is also insufficiently acknowledged or mitigated. In this Personal View, we contend that mandatory risk mitigation measures are necessary, more so in view of the likely increase of sharing of materials and pathogen sequence information under the WHO Pandemic Agreement and the related Pathogen Access and Benefit Sharing framework. Based on a joint reflection of the Institutional Review Board and individual researchers at the Institute of Tropical Medicine in Antwerp, Belgium, we propose a four-step approach to mitigate such risks: prevention or early removal of human genetic sequences, secure storage of samples and data, adaptation of informed consent, and targeted ethics review. This approach should contribute to maintaining ethical integrity, protect the rights of individuals and communities, and bolster public trust in the expanding use of untargeted sequencing in global health research.

Humans↗
PubMedDate not supplied

An emergency medical services transfer authorization center in response to the Toronto severe acute respiratory syndrome outbreak.

OBJECTIVE: To describe the rapid development and implementation of an innovative emergency medical services (EMS) command, control, and tracking system to mitigate the risk of iatrogenic spread of severe acute respiratory syndrome (SARS) among health care facilities, health care workers, and patients in Ontario, Canada, as a result of interfacility patient transfers. METHODS: A working group of stakeholders in health care and transport medicine developed and implemented a medically based command, control, and tracking center for all interfacility (including acute and long-term care) patient transfers in Ontario, Canada. Development and implementation took place in three distinct but overlapping phases: needs assessment, design and implementation, and expansion and ongoing operations. RESULTS: The needs assessment, design, and implementation were completed in less than 48 hours using existing EMS infrastructure and personnel. The center was successfully handling more than 500 requests for interfacility patient transfer per day within 36 hours of operation and more than 1,100 requests per day within two weeks. Expansion into a new physical space enables 40 staff to process up to 1,500 requests per day. There was no reported spread of SARS resulting from interfacility patient transfers since the center began operation on April 1, 2003, and anecdotal evidence demonstrates it identified up to 13 new SARS cases. The center continues to operate as a part of Ontario's commitment as a result of diligence in transport medicine and infection control, even though no new cases of SARS were reported since June 12, 2003. Further study is needed to determine its overall efficacy at risk mitigation. CONCLUSIONS: Rapid establishment of an EMS-based command, control, and tracking center is possible in the setting of a public health emergency. In addition to risk mitigation, this type of center could provide syndromic surveillance in real time and provide the earliest indication of a potential threat to public health in acute and long-term care facilities.

Communicable Disease Control↗
PubMed2006

Methane flux and oxidation at two types of intermediate landfill covers.

Methane emissions were measured on two areas at a Florida (USA) landfill using the static chamber technique. Because existing literature contains few measurements of methane emissions and oxidation in intermediate cover areas, this study focused on field measurement of emissions at 15-cm-thick non-vegetated intermediate cover overlying 1-year-old waste and a 45-cm-thick vegetated intermediate cover overlying 7-year-old waste. The 45 cm thick cover can also simulate non-engineered covers associated with older closed landfills. Oxidation of the emitted methane was evaluated using stable isotope techniques. The arithmetic means of the measured fluxes were 54 and 22 g CH(4) m(-2)d(-1) from the thin cover and the thick cover, respectively. The peak flux was 596 g m(-2)d(-1) for the thin cover and 330 g m(-2)d(-1) for the thick cover. The mean percent oxidation was significantly greater (25%) at the thick cover relative to the thin cover (14%). This difference only partly accounted for the difference in emissions from the two sites. Inverse distance weighing was used to describe the spatial variation of flux emissions from each cover type. The geospatial mean flux was 21.6 g m(-2)d(-1) for the thick intermediate cover and 50.0 g m(-2)d(-1) for the thin intermediate cover. High emission zones in the thick cover were fewer and more isolated, while high emission zones in the thin cover were continuous and covered a larger area. These differences in the emission patterns suggest that different CH(4) mitigation techniques should be applied to the two areas. For the thick intermediate cover, we suggest that effective mitigation of methane emissions could be achieved by placement of individualized compost cells over high emission zones. Emissions from the thin intermediate cover, on the other hand, can be mitigated by placing a compost layer over the entire area.

Air Pollutants↗
PubMed2001

Biochemical properties of heat-treated valvular bioprostheses.

BACKGROUND: Preliminary studies showed that heat treatment of glutaraldehyde preserved valvular bioprostheses mitigates calcification. This study was carried out to define the physicochemical characteristics of the heat-treated tissues to elucidate the mechanism involved in the mitigation. METHODS: Glut bovine pericardium or porcine valve samples were treated at 50 degrees C in a 0.625% glutaraldehyde solution for 2 months. Some samples underwent assay for shrinkage temperature, moisture content, ninhydrin test, and acid hydrolysis, and other samples were incubated in human serum for 3 days and then analyzed by electrophoresis to study protein adsorption. RESULTS: Heat treatment mitigated calcification without adversely affecting shrinkage temperature (84.81 degrees C versus 83.95 degrees C) and moisture content (78.68% versus 78.71%). A significant reduction in free amino groups (0.15 versus 0.37 mol NH2/mol collagen) and a significant increase in resistance to acid hydrolysis were observed. Total protein content was similar, but significant differences were found for four proteins adsorbed in the tissues (167, 45, 11.6, and 10 kDa). CONCLUSIONS: The anticalcification effect of heat treatment may be attributed to structural changes, lipid extraction, increased resistance, and modifications of the type and concentration of the proteins adsorbed in the tissue.

Adsorption↗
PubMed2001

Effect of ethanol and ether in the prevention of calcification of bioprostheses.

BACKGROUND: Lipids play a significant role in the process of calcification of bioprostheses. We assessed whether lipid extraction by ethanol, ether, or a surfactant could mitigate calcification of glutaraldehyde-treated bioprostheses. METHODS: On 200 bovine pericardium samples pretreated with 0.6% glutaraldehyde, lipid extraction was carried out by ethanol, ether, or the tween 80 surfactant, and combinations thereof. The treated tissues were implanted subcutaneously in 50 juvenile rats for 4 and 6 months. Lipids were analyzed by Fourier transform infrared spectrophotometer and chromatography before implantation. Calcium content of implanted tissues was assessed by atomic absorption spectrometer. RESULTS: Ethanol, ether, or surfactant did mitigate calcification. The most efficient pretreatments were the combination of ethanol and surfactant (calcium content: 15.5+/-6.8 microg/mg dry tissue after 6 months implantation) or the combination of ethanol, ether, and surfactant (13.1+/-6.2 microg/mg dry tissue) when compared with surfactant alone (42.9+/-12.7 microg/mg dry tissue). CONCLUSIONS: Ethanol or the combination of ethanol and ether added to the currently used glutaraldehyde-surfactant treatment further mitigates calcification.

Animals↗
PubMed2003

Investigating options for attenuating methane emission from Indian rice fields.

The development of methods and strategies to reduce the emission of methane from paddy fields is a central component of ongoing efforts to protect the Earth's atmosphere and to avert a possible climate change. It appears from this investigation that there can be more than one strategy to contain methane emission from paddy fields, which are thought to be a major source of methane emission in tropical Asia. Promising among the mitigating options may be water management, organic amendments, fertilizer application and selection of rice cultivars. It is always better to adopt multi-pronged strategies to contain CH4 efflux from rice wetlands. Use of fermented manures with low C/N ratio, application of sulfate-containing chemical fertilizers, selection of low CH4 emitting rice cultivars, and implementation of one or two short aeration periods before the heading stage can be effective options to minimize CH4 emission from paddy fields. Among these strategies, water management, which appears to be the best cost-effective and eco-friendly way for methane mitigation, is only possible when excess water is available for reflooding after short soil drying at the right timing and stage. However, in tropical Asia, rice fields are naturally flooded during the monsoonal rainy season and fully controlled drainage is often impossible. In such situation, water deficits during the vegetative and reproductive stage may drastically affect the rice yields. Thus, care must be taken to mitigate methane emission without affecting rice yields.

Agriculture↗
PubMed1999

Contracting-out health care services: a conceptual framework.

Contracting-out has become increasingly prominent in the health-care sector. It has been used in activities ranging from 'internal market' arrangements in which providers compete for funding from government payers to purchases of medical and non-medical inputs by service providers. While contracting-out arrangements for non-medical services have been widely adopted with apparent success, the contracting-out of medical services has met with criticism. Specifically, prominent 'market failures' have been identified which allegedly make contracting-out inefficient and even potentially disruptive to health care delivery. This paper presents and discusses a systematic framework for policymakers to identify and assess potential problems in contracting-out health care services, as well as some generic approaches to mitigating these potential problems. A key to the framework is the notion that conditions contributing to potential market failure problems can often be mitigated by policymakers, and that the strategic choices of policymakers in the 'first stage' of the contracting process should include an analysis of how the contracting-out environment can be changed to mitigate potential market failure problems.

Contract Services↗
PubMed1993

Cerebral resuscitation after cardiac arrest: research initiatives and future directions.

At present, fewer than 10% of cardiopulmonary resuscitation (CPR) attempts prehospital or in hospitals outside special care units result in survival without brain damage. Minimizing response times and optimizing CPR performance would improve results. A breakthrough, however, can be expected to occur only when cerebral resuscitation research has achieved consistent conscious survival after normothermic cardiac arrest (no flow) times of not only five minutes but up to ten minutes. Most cerebral neurons and cardiac myocytes tolerate normothermic ischemic anoxia of up to 20 minutes. Particularly vulnerable neurons die, in part, because of the complex secondary post-reflow derangements in vital organs (the postresuscitation syndrome) which can be mitigated. Brain-orientation of CPR led to the cardiopulmonary-cerebral resuscitation (CPCR) system of basic, advanced, and prolonged life support. In large animal models with cardiac arrest of 10 to 15 minutes, external CPR, life support of at least three days, and outcome evaluation, the numbers of conscious survivors (although not with normal brain histology) have been increased with more effective reperfusion by open-chest CPR or emergency cardiopulmonary bypass, an early hypertensive bout, early post-arrest calcium entry blocker therapy, or mild cerebral hypothermia (34 C) immediately following cardiac arrest. More than ten drug treatments evaluated have not reproducibly mitigated brain damage in such animal models. Controlled clinical trials of novel CPCR treatments reveal feasibility and side effects but, in the absence of a breakthrough effect, may not discriminate between a treatment's ability to mitigate brain damage in selected cases and the absence of any treatment effect. More intensified, coordinated, multicenter cerebral resuscitation research is justified.

Animals↗
PubMed2000

Thiopental combination treatments for cerebral resuscitation after prolonged cardiac arrest in dogs. Exploratory outcome study.

We postulate that mitigating the multifactorial pathogenesis of postischemic encephalopathy requires multifaceted treatments. In preparation for expensive definitive studies, we are reporting here the results of small exploratory series, compared with historic controls with the same model. We hypothesized that the brain damage mitigating effect of mild hypothermia after cardiac arrest can be enhanced with thiopental loading, and even more so with the further addition of phenytoin and methylprednisolone. Twenty-four dogs (four groups of six dogs each) received VF 12.5 min no-flow, reversed with brief cardiopulmonary bypass (CPB), controlled ventilation to 20 h, and intensive care to 96 h. Group 1 with normothermia throughout and randomized group 2 with mild hypothermia (from reperfusion to 2 h) were controls. Then, group 3 received in addition, thiopental 90 mg/kg i.v. over the first 6 h. Then, group 4 received, in addition to group 2 treatment, thiopental 30 mg/kg i.v. over the first 90 min (because the larger dose had produced cardiopulmonary complications), plus phenytoin 15 mg/kg i.v. at 15 min after reperfusion, and methylprednisolone 130 mg/kg i.v. over 20 h. All dogs survived. Best overall performance categories (OPC) achieved (OPC 1 = normal, OPC 5 = brain death) were better in group 2 than group 1 (< 0.05) and numerically better in groups 3 or 4 than in groups 1 or 2. Good cerebral outcome (OPC 1 or 2) was achieved by all six dogs only in group 4 (P < 0.05 group 4 vs. 2). Best NDS were 44 +/- 3% in group 1; 20 +/- 14% in group 2 (P = 0.002); 21 +/- 15% in group 3 (NS vs. group 2); and 7 +/- 8% in group 4 (P = 0.08 vs. group 2). Total brain histologic damage scores (HDS) at 96 h were 156 +/- 38 in group 1; 81 +/- 12 in group 2 (P < 0.001 vs. group 1); 53 +/- 25 in group 3 (P = 0.02 vs. group 2); and 48 +/- 5 in group 4 (P = 0.02 vs. group 2). We conclude that after prolonged cardiac arrest, the already established brain damage mitigating effect of mild immediate postarrest hypothermia might be enhanced by thiopental, and perhaps then further enhanced by adding phenytoin and methylprednisolone.

Animals↗
PubMed2000

Effects of increased oxygen breathing in a volume controlled hemorrhagic shock outcome model in rats.

It is believed that victims of traumatic hemorrhagic shock (HS) benefit from breathing 100% O(2). Supplying bottled O(2) for military and civilian first aid is difficult and expensive. We tested the hypothesis that increased FiO(2) both during severe volume-controlled HS and after resuscitation in rats would: (1) increase blood pressure; (2) mitigate visceral dysoxia and thereby prevent post-shock multiple organ failure; and (3) increase survival time and rate. Thirty rats, under light anesthesia with halothane (0. 5% throughout), with spontaneous breathing of air, underwent blood withdrawal of 3 ml/100 g over 15 min. After HS phase I of 60 min, resuscitation phase II of 180 min with normotensive intravenous fluid resuscitation (shed blood plus lactated Ringer's solution), was followed by an observation phase III to 72 h and necropsy. Rats were randomly divided into three groups of ten rats each: group 1 with FiO(2) 0.21 (air) throughout; group 2 with FiO(2) 0.5; and group 3 with FiO(2) 1.0, from HS 15 min to the end of phase II. Visceral dysoxia was monitored during phases I and II in terms of liver and gut surface PCO(2) increase. The main outcome variables were survival time and rate. PaO(2) values at the end of HS averaged 88 mmHg with FiO(2) 0.21; 217 with FiO(2) 0.5; and 348 with FiO(2) 1. 0 (P<0.001). During HS phase I, FiO(2) 0.5 increased mean arterial pressure (MAP) (NS) and kept arterial lactate lower (P<0.05), compared with FiO(2) 0.21 or 1.0. During phase II, FiO(2) 0.5 and 1. 0 increased MAP compared with FiO(2) 0.21 (P<0.01). Heart rate was transiently slower during phases I and II in oxygen groups 2 and 3, compared with air group 1 (P<0.05). During HS, FiO(2) 0.5 and 1.0 mitigated visceral dysoxia (tissue PCO(2) rise) transiently, compared with FiO(2) 0.21 (P<0.05). Survival time (by life table analysis) was longer after FiO(2) 0.5 than after FiO(2) 0.21 (P<0. 05) or 1.0 (NS), without a significant difference between FiO(2) 0. 21 and 1.0. Survival rate to 72 h was achieved by two of ten rats in FiO(2) 0.21 group 1, by four of ten rats in FiO(2) 0.5 group 2 (NS); and by four of ten rats of FiO(2) 1.0 group 3 (NS). In late deaths macroscopic necroses of the small intestine were less frequent in FiO(2) 0.5 group 2. We conclude that in rats, in the absence of hypoxemia, increasing FiO(2) from 0.21 to 0.5 or 1.0 does not increase the chance to achieve long-term survival. Breathing FiO(2) 0.5, however, might increase survival time in untreated HS, as it can mitigate hypotension, lactacidemia and visceral dysoxia.

Animals↗
PubMed2002

Characterization of visual phenomena with the Array multifocal intraocular lens.

PURPOSE: To characterize the visual sensations reported after bilateral implantation of the Array multifocal intraocular lens (IOL) (Allergan Surgical) and evaluate the means to mitigate unwanted visual sensations. SETTING: Surgery centers in Kansas City, Missouri, and Lake Worth, Florida, USA. METHODS: A retrospective parallel-group assessment of subjective nighttime visual sensations was conducted in 22 patients who had bilateral implantation of the Array multifocal IOL. Thirteen patients were recruited from a small subset of patients who were dissatisfied with the Array because of unwanted visual sensations (UVS group). The parallel group included 9 patients who were satisfied with the Array and not bothered by visual sensations (satisfied group). The primary endpoint was the patient's characterization of visual phenomena under simulated nighttime conditions. The secondary endpoint was the effect of adding trial lenses of -0.50 diopter (D) and -1.00 D to the patient's distance spectacle correction. RESULTS: Most patients reported that the simulation produced visual sensations similar to their real-life experiences. Patients in the UVS group reported the visual sensations as large starbursts and somewhat spoke-like starbursts with fine lines. Patients in the satisfied group reported them as blurred large or small starbursts. A few reported a color variance and finer quality to the starburst in real life. Visual phenomena were generally mitigated by the addition of a -0.50 D or -1.00 D lens. CONCLUSIONS: Both study groups reported similar visual phenomena. The difference between those who were bothered by the visual sensations and those who were not appears to be a function of individual tolerance. The visual sensations may be mitigated with minus-lens overcorrection.

Aged↗
PubMedDate not supplied

Disasters and development: Part 2: understanding and exploiting disaster-development linkages.

Disasters can impede the effectiveness of development resource allocation. The damage sustained from an event can be classified into four categories: (1) Loss of resources; (2) Interruption of programs and switching of crucial resources to other, shorter-term needs; (3) Negative impacts upon investment climates; and/or (4) Disruption of the non-formal sector (local businesses). Disasters have a particularly destructive economic impact in areas in which there are few alternatives for assets that are destroyed or in areas in which the resources already are at critical levels. Development processes can both increase and/or decrease the vulnerability of a society to hazards. There are dearly established linkages between poverty, marginalization, over-population, and vulnerability. To a large extent, vulnerability derives from poverty. The poor are more likely to live in vulnerable areas (slopes prone to landslides, flood plains, marginal agricultural land), have difficulty accessing education and information, have fewer assets to invest in resources to reduce vulnerability, and are more prone to become malnourished and have chronic illnesses that predispose them to injury and death. Development may be associated with the production of new hazards accepted by a society because the perceived benefits of the development project far exceed the relative risk associated with the project. Therefore, risk assessments must be part of any program planning and evaluation. Training and education are of critical importance in preventing increased vulnerability as a result of development strategies. Development also can progress in a manner that will result in mitigation of the impacts of an event on a given society (increase absorbing capacity and/or buffering capacity, elimination of hazards or the risk of them producing a disaster). Such mitigation measures can be either structural or nonstructural. There exists a wide range of options for incorporating mitigation measures in development projects. Two case studies provide exercises that incorporate the concepts provided in this discussion: (1) The 1985 earthquake in Mexico City; and (2) Agricultural development in northern Sudan.

Agriculture↗
PubMedDate not supplied

Disasters and development: Part 2: Understanding and exploiting disaster-development linkages.

This lesson is a continuation of Disasters and Development: Part 2: Understanding and Exploiting Disaster-Development Linkages published in Prehospital and Disaster Medicine in Volume 17, Number 3. It identifies the goals of a specific damage mitigation project that can be incorporated into a regular development project and the mechanisms for obtaining the mitigation component of such a project. Mechanisms for assessing the success of such a project are discussed. It stresses the importance of the application of building codes, associated training programs, and more extensive use of zoning regulations in urban development that decrease the population at risk and the likelihood of damage to industrial facilities. Disasters can elevate the development potential of a society at risk for damage from a hazard. The political impact of damage and disruption can be a catalyst for change. Development opportunities often are compromised because of an excessive focus on relief assistance. Interventions designed to mitigate the damage from a given hazard are particularly effective when they focus on areas at particularly high risk for actualization of the hazard. Support from the private sector, including the non-formal sector, is a key element of successful reconstruction management. The period of recovery is an opportunity for general assistance to government with administrative procedures, including enhanced management training programs.

Disaster Planning↗
PubMed2003

Assessment of potential carbon dioxide reductions due to biomass-coal cofiring in the United States.

Cofiring biomass with coal in existing power plants offers a relatively inexpensive and efficient option for increasing near-term biomass energy utilization. Potential benefits include reduced emissions of carbon dioxide, sulfur, and nitrogen oxides and development of biomass energy markets. To understand the economics of this strategy, we develop a model to calculate electricity and pollutant mitigation costs with explicit characterization of uncertainty in fuel and technology costs and variability in fuel properties. The model is first used to evaluate the plant-level economics of cofiring as a function of biomass cost. It is then integrated with state-specific coal consumption and biomass supply estimates to develop national supply curves for cofire electricity and carbon mitigation. A delivered cost of biomass below 15 dollars per ton is required for cofire to be competitive with existing coal-based generation. Except at low biomass prices (less than 15 dollars per ton), cofiring is unlikely to be competitive for NOx or SOx control, but it can provide comparatively inexpensive control of CO2 emissions: we estimate that emissions reductions of 100 Mt-CO2/year (a 5% reduction in electric-sector emissions) can be achieved at 25 +/- 20 dollars/tC. The 2-3 year time horizon for deployment--compared with 10-20 years for other CO2 mitigation options--makes cofiring particularly attractive.

Air Pollutants↗
PubMed2005

Can reducing black carbon emissions counteract global warming?

Field measurements and model results have recently shown that aerosols may have important climatic impacts. One line of inquiry has investigated whether reducing climate-warming soot or black carbon aerosol emissions can form a viable component of mitigating global warming. We review and acknowledge scientific arguments against considering aerosols and greenhouse gases in a common framework, including the differences in the physical mechanisms of climate change and relevant time scales. We argue that such a joint consideration is consistent with the language of the United Nations Framework Convention on Climate Change. We synthesize results from published climate-modeling studies to obtain a global warming potential for black carbon relative to that of CO2 (680 on a 100 year basis). This calculation enables a discussion of cost-effectiveness for mitigating the largest sources of black carbon. We find that many emission reductions are either expensive or difficult to enact when compared with greenhouse gases, particularly in Annex I countries. Finally, we propose a role for black carbon in climate mitigation strategies that is consistent with the apparently conflicting arguments raised during our discussion. Addressing these emissions is a promising way to reduce climatic interference primarily for nations that have not yet agreed to address greenhouse gas emissions and provides the potential for a parallel climate agreement.

Air Pollution↗
PubMed2004

Peroxidase-catalyzed coupling of phenol in the presence of model inorganic and organic solid phases.

Peroxidase-catalyzed oxidative coupling reactions of phenol in aqueous systems variously containing silica sand, cellulose, lignin, and polymethylstyrene were investigated. These four solid phase materials represent a broad spectrum of different natural geosorbent types in terms of their physicochemical characteristics. Each solid was found to influence peroxidase-catalyzed phenol coupling, either by mitigation of enzyme inactivation, by participation in cross-coupling, or by a combination of these two activities. Mitigation of enzyme inactivation was observed for those three of the four model solids found to adsorb the enzyme effectively; i.e., cellulose, silica sand, and lignin. Two solids, polymethylstyrene and lignin, were found to participate significantly in cross-coupling reactions. It is postulated that relatively hydrophilic solids can mitigate peroxidase inactivation by forming enzyme-solid associations. Aromatic structures or unsaturated C-C bonds were found to be features of the solid-phase materials that allowed them to participate in cross-coupling. The results have important implications for process feasibility assessment and the engineering design of soil/sediment remediation systems employing enzymatic coupling schemes.

Biodegradation, Environmental↗
PubMed1996

Implication of nitric oxide synthase activity in the genesis of water immersion stress-induced gastric lesions in rats: the protective effects of FK506.

BACKGROUND: Nitric oxide (NO) is a potent cytoprotective substance of gastric mucosa. FK506, an immunosuppressive drug, shows anti-gastric ulcer effects equivalent to famotidine, an H2 blocker, in rats. This study was designed to evaluate the cytoprotective mechanism of FK506 on gastric mucosa in relation to the changes in NO synthase activity. METHODS: Gastric lesions were induced in rats by water immersion stress. Changes in NO synthase activity during water immersion stress treatment, and effects of FK506 on NO synthase activity were determined enzymatically. Gastric mucosal interleukin (IL)-1 beta and IL-2 were measured by immunoradiometric assay. Gastric mucosal blood flow was measured by hydrogen gas clearance technique. RESULTS: FK506 mitigated gastric lesions developed by water immersion stress. Stress-induced lesions were exacerbated by NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthase, while sodium nitroprusside, a NO donor, mitigated the lesions. Water immersion stress increased NO synthase activity in the early phase (0.5 h after stress treatment) and decreased it in the late phase (6 h after). Decrease in NO synthase activity in the late phase was significantly mitigated by FK506, though it did not affect changes in NO synthase activity in the early phase. Water immersion stress increased gastric mucosal IL-1 beta and IL-2 contents 6 h after stress treatment, and these increases were prevented by FK506. FK506 itself did not affect gastric mucosal blood flow. L-NMMA treatment significantly decreased gastric mucosal blood flow. In contrast, gastric mucosal blood flow was significantly increased by sodium nitroprusside. CONCLUSIONS: Increase in NO synthase activity might contribute to cytoprotection, and a decrease in activity might be a harmful factor for the gastric mucosa. Preservation of NO synthase activity by FK506 might be involved in FK506's protective effects on the gastric mucosa.

Animals↗
PubMed2002

Management of intrathecal catheter-tip inflammatory masses: a consensus statement.

OBJECTIVES: In a companion article, we synthesized current clinical and preclinical data to formulate hypotheses about the etiology of drug administration catheter-tip inflammatory masses. In this article, we communicate our recommendations for the detection, treatment, mitigation, and prevention of such masses. METHODS: We reviewed published and unpublished case reports and our own experiences to find methods to diagnose and treat catheter-tip inflammatory masses in a manner that minimized adverse neurological sequelae. We also formulated hypotheses about theoretical ways to mitigate, and possibly, prevent the formation of such masses. RESULTS: Human cases have occurred only in patients with chronic pain who received intrathecal opioid drugs, alone or mixed with other drugs, or in patients who received agents that were not labeled for long-term intrathecal use. Most patients had noncancer pain owing to their large representation among the population with implanted pumps. Such patients also had a longer life expectancy and exposure to intrathecal drugs, and they received higher daily doses than patients with cancer pain. Clues to diagnosis included the loss of analgesic drug effects accompanied by new, gradually progressive neurological symptoms and signs. When a mass was diagnosed before it filled the spinal canal or before it caused severe neurological symptoms, open surgery to remove the mass often was not required. Anecdotal reports and the authors' experiences suggest that cessation of drug administration through the affected catheter was followed by shrinkage or disappearance of the mass over a period of 2-5 months. CONCLUSIONS: Attentive follow-up and maintenance of an index of suspicion should permit timely diagnosis, minimally invasive treatment, and avoidance of neurological injury from catheter-tip inflammatory masses. Whenever it is feasible, positioning the catheter in the lumbar thecal sac and/or keeping the daily intrathecal opioid dose as low as possible for as long possible may mitigate the seriousness, and perhaps, reduce the incidence of such inflammatory masses.

Journal Article↗