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PubMed2003

The effect of anemia treatment on selected health-related quality-of-life domains: a systematic review.

BACKGROUND: Anemia is a reduction in the oxygen-carrying capacity of red blood cells that results in a variety of symptoms, including dyspnea, headaches, light-headedness, and fatigue. Although anemia has been associated with reduced health-related quality of life (HRQoL), its treatment has not yet been consistently shown to improve HRQoL. OBJECTIVE: This systematic review of the literature was conducted to determine whether the treatment of anemia improves HRQoL domains, regardless of the type of underlying disease. METHODS: Data for this review were drawn from the clinical trial databases from 2 previous systematic literature reviews of erythropoiesis-stimulating protein treatment for renal insufficiency- and cancer-related anemia, both spanning the period January 1, 1980, through December 31, 2001. MEDLINE, Cancerlit, and Current Contents/Clinical Medicine were searched using the combined terms erythropoietin, kidney failure, neoplasms, and anemia. The reference lists of all identified articles were searched manually for additional relevant papers. The review included prospective studies that reported both HRQoL and hematocrit (Hct) in patients with cancer or renal insufficiency who received treatment for anemia with an erythropoiesis-stimulating protein. HRQoL was categorized by domain (overall, energy/fatigue, physical, activity); changes in HRQoL domains were expressed as effect sizes and meta-analyzed, as were correlation coefficients. The effects on HRQoL of dropout rate, study duration, baseline Hct, and change in Hct were examined in meta-regression analyses. RESULTS: Sixteen studies each were identified in patients with renal insufficiency (N = 2253) and patients with cancer (N = 10,695). The treated groups included 11,710 patients, and the control groups included 1238 patients. The baseline Hct in all treated groups averaged 26.0%: 28.3% in the group with cancer and 24.4% in the group with renal insufficiency. The mean improvement in Hct from baseline to the end of treatment was 8.3% (range, 1.0%-16.5%) in treated patients and 1.0% (range, 0.0%-3.3%) in controls. The Hct changes were similar in treated patients with cancer and treated patients with renal insufficiency, as was the HRQoL effect size (0.43). Dropout rate and study duration were not significant predictors of HRQoL changes, but change in Hct was a significant predictor in both conditions. Meta-analysis of the correlation coefficients, adjusting for HRQoL domains, showed a consistent and significant positive correlation between change in Hct and change in HRQoL (P < 0.001). CONCLUSION: The consistency in both direction and magnitude of effect across many studies and thousands of patients supports the hypothesis that treatment of anemia with erythropoiesis-stimulating protein improves selected HRQoL domains in patients with renal insufficiency- or cancer-related anemia.

Anemia↗
PubMed2000

Investigation of a ponding irrigation system to recycle agricultural wastewater.

This article presents the results of natural carrying capacity of ponding irrigation system in Taoyuan agricultural zone, Taiwan. Both the systematic water quality and the ponding effects were examined. The ponding irrigation system included a flow channel and storage ponds. The data showed that most water characteristics deteriorated gradually from upper- to down-stream in the flow channel and the flow channel was not attributed to any self-purification in agricultural returning water practically. On the other hand, the results of storage ponds indicated that they can provide a natural treatment (i.e., the outlet water quality of the ponds is more desirable than that of the inlet). Consequently, the ponding irrigation system offers the natural self-purification in ponds to reuse and recycle the returning agricultural wastewater and to extend the irrigation capacity and efficiency.

Agriculture↗
PubMed1994

The acute effect of smoking on retinal blood flow in subjects with and without diabetes.

PURPOSE: This study investigates the effect of smoking on retinal blood flow and autoregulation in smokers with and without diabetes. METHODS: Eleven patients with diabetes mellitus and ten control subjects were investigated. Laser Doppler velocimetry and retinal photography were used to measure retinal blood flow; vascular autoregulation was assessed with 60% oxygen breathing. These procedures were performed before and after smoking. RESULTS: Both groups demonstrated a significant increase in heart rate and systolic and diastolic blood pressure (P < 0.01). In both groups, smoking caused a significant decrease in retinal blood flow: 9.6% +/- 12% in the control group (P < 0.05) and 16.4% +/- 13.8% in the diabetic group (P < 0.01). The pre-smoking oxygen reactivity was comparable in both groups (P = 0.5); 27.9% +/- 3.3% and 32.0% +/- 5.0% in the control and diabetic groups, respectively. After smoking, oxygen reactivity was reduced significantly in the control group to 9.6% +/- 4.0% (P = 0.002) and eliminated in the patients with diabetes. CONCLUSIONS: This study shows that smoking reduces retinal blood flow and the ability of the retinal vessels to autoregulate to hyperoxia; these effects are likely to be due to the vasoconstrictive effect of nicotine, which is mediated through activation of the sympathetic system. Smoking has been shown previously to increase the level of carboxyhemoglobin, thereby reducing the oxygen-carrying capacity of blood, which, when associated with the reduced blood flow shown in the current study, may reduce retinal oxygen delivery. Hypoxia is a major factor in the progression of diabetic retinopathy; therefore, smoking may exert a detrimental influence, which may be compounded further by the additional effect smoking has on autoregulation.

Adult↗
PubMed2001

Direct and indirect effects of sublethal toxicant exposure on population dynamics of freshwater rotifers: a modeling approach.

Ecotoxicological assessments commonly consider the direct effects of anthropogenic toxicants on the survival, growth, and reproduction of organisms. However, toxicants also may have indirect effects on aquatic communities by altering species interactions such as predation and competition. Such indirect effects are often mediated by changes in animal behavior, and contribute to uncertainty in predicting the environmental effects of toxicants. In an attempt to better understand indirect effects, a modeling approach was used to simulate the population dynamics of the predatory rotifer Asplanchna girodi and six prey species of herbivorous rotifers in response to sublethal concentrations (110, 190 or 330 mg/l) of pentachlorophenol (PCP). Simulations were performed assuming three different toxicant effect scenarios: behavioral toxicity alone, reproductive toxicity alone, or both behavioral and reproductive toxicity. Population growth rates (G(r)), maximum population densities (D(max)), and the percent of carrying capacity at D(max) (%K) were calculated for A. girodi and each prey species for each effect scenario and toxicant concentration. Similar qualitative results were obtained regardless of which prey species was exploited by A. girodi. Toxicant effects on predator and prey population densities appeared to be the dominant cause of both direct and indirect toxicant effects, and behavioral toxicity was a redundant endpoint relative to reproductive toxicity. These results suggest that assessing toxicant effects on the population growth of individual species may provide sufficient data to predict toxicant effects on species interactions as well.

Animals↗
PubMed2001

Activation of circulating platelets and platelet response to activating agents in children with cyanotic congenital heart disease: their relevance to palliative systemic-pulmonary shunt.

Abnormal platelet function has been hypothesised to play a role in the haemostatic abnormalities in cyanotic congenital heart disease (CCHD) patients. Using whole blood flow cytometry we found that platelets from cyanotic patients were hyperreactive and we related such hyperreactivity directly to young age, unoperated state, high haematocrit, reduced saturation with oxygen and low platelet count. Circulating platelets from CCHD children showed significantly enhanced P-selectin expression (P<0.004) and remained more reactive to 0.2 IU/ml thrombin, 1-8 microM TRAP and 2-4 microM ADP (P<0.04), especially in younger (0-3-year-olds) patients. Such a platelet 'priming' largely concerned CCHD children who were not subjected to modified Blalock-Taussig shunts in the past (non-MBTS). Only non-MBTS cyanotic children, but not MBTS-operated patients, showed significantly higher platelet reactivity compared to controls in response to ADP or 1 microM TRAP with respect to P-selectin expression (p<0.05) and in response to all examined agonists with respect to GPIb expression (P<0.045). The enhanced P-selection expression in MBTS-operated CCHD children and reduced GPIb expression in non-MBTS patients, especially in younger patients, were positively associated with the occurrence of the polymorphic variant Pl(A2) of platelet membrane glycoprotein IIIa gene. Altered blood morphology parameters (elevated RBC, Hb, Hct and MCHC, for all P<0.0005) in CCHD children correlated with the enhanced degranulation of circulating blood platelets and their hyperreactivity in response to some agonists (P<0.05). Overall, our data encourage the reasoning that circulating platelets are remarkably hyperreactive in non-MBTS cyanotic children, which are at higher risk to often encounter platelets activation in circulation. It seems unlikely that the apparently unchanged platelet reactivity in MBTS-operated children is due to the advantageous effects of the shunt, since these patients showed neither altered haematological parameters nor improved oxygen carrying capacity. Otherwise, it may rather result from more frequent episodes of platelet degranulation and preactivation in the past, and/or post-operative enhanced platelet consumption.

Blood Vessel Prosthesis↗
PubMed1997

Progress in development of herpes simplex virus gene vectors for treatment of rheumatoid arthritis.

Arthritis is presently incurable and poorly treatable, but there are good grounds for expecting gene therapy to improve matters considerably. Although local ex vivo delivery of anti-arthritic genes to the synovial lining of joints has shown considerable promise, intraarticular gene delivery may be desirable. Herpes simplex virus (HSV) may be a viable vector for in vivo transfer of anti-arthritic genes to joints. HSV has the advantages of high infectivity, large carrying capacity and high titer. The large packaging capacity would permit the inclusion of multiple anti-arthritic genes and necessary regulatory elements. Recombinant vectors produced by this laboratory infect synovial cells efficiently, permitting prolonged expression of transgenes in vitro and in vivo without evidence of cytotoxicity. Further improvements to this vector system include taking advantage of an endogenous HSV 'stealthing' gene, ICP47, which interferes with formation of antigen-class I complexes. Inclusion of inducible promoters to appropriately regulate expression of anti-arthritic genes should further improve this system.

Journal Article↗
PubMed2000

Tissue perfusion and oxygenation with blood substitutes.

As an alternative to transfusion of red blood cells, intravenously (iv) administered artificial oxygen (O(2)) carriers are intended to increase the reduced O(2) carrying capacity of blood in the case of acute severe anemia, i.e. hemorrhagic shock or extreme normovolemic hemodilution (ANH). Actually, two groups of artificial O(2) carriers are investigated: ultrapurified, stroma-free hemoglobin solutions (SFH) of human or bovine origin and synthetically produced perfluorocarbons (PFC). SFH may be administered in large amounts and are suitable for 1:1 replacement of blood losses in case of hemorrhage as well as for isovolemic exchange of blood during ANH. In both situations SFH solutions effectively restore (hemorrhagic shock) and maintain (extreme ANH) tissue oxygenation despite extremely low hematocrit values. The vasopressor property of the isolated Hb molecule leads to a species-dependent (rodent>pig>human) increase in systemic and pulmonary vascular resistance, but leaves overall distribution of cardiac output uninfluenced. Due to the particulate nature of PFC emulsions, iv administration has to be restricted to small doses (3-4.5 ml/kg body weight for the actually investigated 60% w/v perflubron emulsion) in order to avoid overload of the reticuloendothelial system. Thus PFC emulsions are unsuitable for isovolemic blood replacement in hemorrhagic shock or ANH. Low-dose iv PFC administration in already hemodiluted subjects, however, creates an additional margin of safety to guarantee adequate tissue oxygenation which allows for further, extreme ANH, without risking tissue hypoxia.

Animals↗
PubMed1995

Modern veterinary blood banking practices and their applications in companion animal practice.

There are two main reasons for blood component therapy: the need for an increase in oxygen-carrying capacity and improved hemostasis. Additionally, blood component therapy is used to increase plasma protein concentrations. Component therapy entails separating whole blood into its cellular and plasma components and administering the appropriate blood component based on the patient's needs. General considerations such as compatibility, defined expectations of benefits, and topics including specific disease screening, preparation of blood components, preparation of blood products for administration, and typing and crossmatching in relation to blood component therapy and its application in companion animal practice are discussed.

Animals↗
PubMed1993

Cyanide and methemoglobin kinetics in smoke inhalation victims treated with the cyanide antidote kit.

STUDY OBJECTIVE: To evaluate serial cyanide, methemoglobin, and carbon monoxide levels in smoke inhalation patients. SETTING: Regional poison center and regional toxicology treatment center. PARTICIPANTS: Seven critically ill smoke inhalation patients referred to the regional poison center. INTERVENTIONS: Peak level and half-life were determined by obtaining serial carboxyhemoglobin, cyanide, and methemoglobin levels. RESULTS: The mean observed half-life of cyanide was 3.0 +/- 0.6 hours. Methemoglobinemia was evaluated in four patients after sodium nitrite administration. The peak measured methemoglobin levels (mean, 10.5% +/- 2%; range, 7.9% to 13.4%) did not occur until a mean of 50 minutes (range, 35 to 70 minutes) following administration of sodium nitrite. The total oxygen-carrying capacity reduced by the combination of carboxyhemoglobin and methemoglobin was never more than 21% (range, 10% to 21%) in this series. CONCLUSION: The administration of sodium nitrite to smoke inhalation patients in the presence of concomitant carbon monoxide poisoning may be relatively safe.

Adult↗
PubMed1985

Red cell substitutes: an update.

The two acellular oxygen carriers currently being evaluated as red cell substitutes are hemoglobin solutions and fluorocarbon emulsions. We have shown that both products can maintain normal levels of oxygen consumption, CO2 production, and circulatory dynamics in primates in the virtual absence of the red blood cell. Although each solution thus satisfies the most important criteria for a red cell substitute, development continues with both products. The clinical trials with the fluorocarbons have been discontinued due to the lack of efficacy of Fluosol-DA--20% in the setting of acute blood loss. Our current hemoglobin preparation is a polymerized, pyridoxylated product that has a normal oxygen-carrying capacity. Clinical testing must await further evaluation of the safety and efficacy of this product. Alternative uses for both of these oxygen carriers continue to be explored, and may eventually be the area of their greatest utility in the clinical setting.

Animals↗
PubMed2002

Dynamics of change in local physician supply: an ecological perspective.

The purpose of this study is to employ an ecological framework to identify factors that have an impact on change in local physician supply within the USA. A particular specialty type of patient care physicians in a local market is defined as a physician population. Four physician populations are identified: generalists, medical specialists, surgical specialists, and hospital-based specialists. Based on population ecology theory, the proposed framework explains the growth of a particular physician population by four mechanisms: the intrinsic properties of this physician population; the local market's carrying capacity, which is determined by three environmental dimensions (munificence, concentration, diversity); competition within the same physician population; and interdependence between different physician populations. Data at the level of Metropolitan Statistical Areas (MSAs) were compiled from the US Area Resources File, the American Hospital Association Annual Surveys of Hospitals, the American Medical Association Census of Medical Groups, the InterStudy National HMO Census, and the US County Business Patterns. Changes in the number and percentage of physicians in a particular specialty population from 1985 to 1994 were regressed, respectively, on 1985-94 changes in the explanatory variables as well as their levels in 1985. The results indicate that the population ecology framework is useful in explaining dynamics of change in the local physician workforce. Variables measuring the three environmental dimensions were found to have significant, and in some cases, differential effects on change in the size of different specialty populations. For example, both hospital consolidation and managed care penetration showed significant positive eflects on growth of the generalist population but suppressing effects on growth of the specialist population. The percentage of physicians in a particular specialty population in 1985 was negatively related to change in the size of that specialty population between 1985 and 1994, suggesting the existence of competition. Overall, the findings of this study facilitate a better understanding of the complexity of physician workforce supply.

Catchment Area, Health↗
PubMed1996

Erythropoietin: physico- and biochemical analysis.

A hormone, erythropoietin, mainly produced in adult kidneys and fetal livers, acts on bone marrow erythroid progenitor cells to regulate the production of erythrocyte in mammals. As a result, the oxygen carrying capacity of blood increases and the increased oxygen supply raises the cardiac function and physiological working capacity. Erythropoietin is possibly misused by athletes in sports for the purpose of improving performance. Presently there is no discernible and specific method to identify erythropoietin administration for doping control. To address this practical problem, this paper presents a summary of the applications of analytical biotechnology, especially the structural characterization of erythropoietin.

Animals↗
PubMed2000

Methods of aggregation of variables in population dynamics.

In ecology, we are faced with modelling complex systems involving many variables corresponding to interacting populations structured in different compartmental classes, ages and spatial patches. Models that incorporate such a variety of aspects would lead to systems of equations with many variables and parameters. Mathematical analysis of these models would, in general, be impossible. In many real cases, the dynamics of the system corresponds to two or more time scales. For example, individual decisions can be rapid in comparison to growth of the populations. In that case, it is possible to perform aggregation methods that allow one to build a reduced model that governs the dynamics of a lower dimensional system, at a slow time scale. In this article, we present a review of aggregation methods for time continuous systems as well as for discrete models. We also present applications in population dynamics. A first example concerns a continuous time model of a single population distributed on a system of two connected patches (a logistic source and a sink), by fast migration. It is shown that under a certain condition, the total equilibrium population can be larger than the carrying capacity of the logistic source. A second example concerns a discrete model of a population distributed on two patches, still a source and a sink, connected by fast migration. The use of aggregation methods permits us to conclude that density-dependent migration can stabilize the total population.

Animals↗
PubMed2001

Pediatric resuscitation in the operating room.

The resuscitation of pediatric patients undergoing anesthesia involves appropriate administration of fluid and blood products and stabilization of vital signs. Crystalloid is first-line therapy for fluid resuscitation, and should be given with awareness of its potential dilution of the child's hematocrit. Many alternatives to homologous blood transfusions now exist, however, when necessary for increasing oxygen-carrying capacity or treating coagulopathy benefits likely outweight the risks. The risks for such transfusion include infectious, hemolytic, metabolic, and immunologic effects. When fluid and blood administration does not stabilize the patient, the differential diagnosis of hypotension, arrest, or arrhythmias must include medication errors, anesthetic overdose, electrolyte disturbances, hypoxemia, ventilatory problems, and surgical insults, including medications given in the operative field. Resuscitation should include treatment of hypocalcemia and hyperkalemia, chest compressions, and the administration of epinephrine when necessary.

Cardiopulmonary Resuscitation↗
PubMed2000

Hematologic management of gastrointestinal bleeding.

The hematologic management of gastrointestinal (GI) bleeding requires evaluation of the underlying cause of bleeding, associated diseases that can exacerbate the bleeding, and identification of related and unrelated coagulation abnormalities. Erythrocyte transfusions are given to increase oxygen carrying capacity; however, there is limited information on the level of anemia that places a patient at increased risk of adverse events after a GI bleed and when patients should receive erythrocyte transfusion. Isolated thrombocytopenia is uncommon in patients with GI bleeding, and there is little evidence documenting the degree of thrombocytopenia associated with an increased risk of bleeding. Platelets are often administered when the count is 50,000 per cu/mL in a bleeding patient. The coagulopathy of liver disease is the most common abnormality seen in the setting of GI bleeding. Fresh-frozen plasma (FFP) should be given in a dose equivalent to the underlying abnormality and the common practice of administering 2 units of FFP is often insufficient in a bleeding patient.

Clinical Trials as Topic↗
PubMed1987

Rheology of the absolute polycythaemias.

The absolute polycythaemias include all patients who have a raised red cell mass. They may be divided by clinical and laboratory investigation into: primary proliferative polycythaemia (polycythaemia rubra vera), secondary polycythaemias, and idiopathic erythrocytosis. In vitro, the PCV is the single most important determinant of whole blood viscosity with the most marked effects at low shear rates. Yield stress is also dominantly influenced by PCV. Thus in the absolute polycythaemias, from whatever cause, whole blood viscosity and yield stress are high. However, flow conditions in vivo are much more complex than those usually used in in-vitro measurements. Under normal physiological conditions, whole blood viscosity probably does not determine flow in vivo. The observed in-vitro changes are only of relevance in vivo when local or general abnormalities of flow occur. In primary proliferative polycythaemia (PPP) and idiopathic erythrocytosis, presentation with ischaemia or thrombosis (either arterial or venous) is common, and the cerebral circulation is at particular risk. The incidence of vascular occlusion is positively correlated with the PCV. There is an inverse correlation between PCV and cerebral blood flow (CBF), with untreated patients having low CBF values. This is probably a 'physiological' change related to the increased oxygen carrying capacity at high PCV values. However, in many patients, cerebral oxygen carriage actually increases on reduction of the PCV to normal. This explains the improvement in cerebral ischaemic symptoms and mental performance which may be observed following treatment. Platelet contact and adhesion to the vessel wall are increased at high PCV values and, combined with the lower blood flow in both the arteries and veins, tend to favour thrombus formation. Ischaemia causes vessel dilatation but when this is maximal the high whole-blood viscosity demonstrated in vitro is a major determinant of flow. Hence in man and experimental animals, as demonstrated in the brain, the area of ischaemia or non-perfusion following arterial occlusion is greatest at high PCV values. Patients with polycythaemia due to hypoxic lung disease have a poor prognosis. The hypoxic pulmonary vasoconstriction combined with the high blood viscosity causes an increase in pulmonary vessel resistance. PCV reduction of 0.50-0.52 leads to an improvement in work performance and mental alertness, and reduction in pulmonary vascular resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Flow Velocity↗
PubMed1990

Autotransfusion during aorto-iliac surgery.

Red blood cell (RBC) quality and function during autotransfusion with the Solcotrans system were studied. Up to 64% (mean 999.5 +/- 310 ml) of the total volume of blood lost (mean 1895 +/- 707 ml) during operation in 10 patients undergoing elective abdominal aortic surgery was salvaged. No patient received homologous blood during surgery. Haemoglobin (Hb) and Haematocrit (PCV) values decreased but within acceptable limits. No evidence of DIC was found and renal function was unaffected. Mechanical and functional damage to the RBC was minimal and erythrocyte oxygen-carrying capacity was excellent. 2,3-DPGRBC concentration and RBC reduced glutathion were normal. The device was easy to handle and technical problems were not encountered. It was accurate in salvaging blood although the need for homologous blood was not entirely eliminated since four patients received homologous blood products in the postoperative period. No adverse clinical events occurred.

Aged↗
PubMed2000

Local delivery of nadroparin via hydrogel-coated angioplasty balloon: effect on platelet deposition and smooth muscle cell proliferation--an experimental study.

PURPOSE: To assess the feasibility of intravascular delivery of nadroparin, a low-molecular-weight heparin, via hydrogel-coated angioplasty balloons, and the effects of nadroparin delivered in this manner on platelet deposition and smooth muscle cell (SMC) proliferation. MATERIALS AND METHODS: Tritiated nadroparin was used to determine the nadroparin-carrying capacity of the hydrogel-coating, kinetics of release from the balloons, and, in four pigs, delivery of the nadroparin to the iliac arterial wall. Platelet deposition in nadroparin-treated iliac arteries versus contralateral iliac arteries dilated with saline-loaded, hydrogel-coated balloons was quantified in seven pigs using 111Indium-labeled platelets. Smooth muscle cell proliferation in nadroparin and saline-treated iliac arteries in 10 pigs was evaluated 7 days after angioplasty with use of proliferating cell nuclear antigen. RESULTS: Approximately 98 international units of nadroparin were delivered by the hydrogel-coated balloon, the majority to the angioplasty site and distal vessel. There was a trend toward decreased platelet deposition in nadroparin-treated arteries, but statistical significance was not achieved (P = .1563). Medial SMC proliferation was decreased in the nadroparin-treated arteries in nine of 10 pigs (P = .0137). CONCLUSIONS: Hydrogel-coated balloons may be used to deliver nadroparin to the arterial wall, with measurable levels of the drug delivered to the site of angioplasty, and with resultant decrease in SMC proliferation.

Angioplasty, Balloon↗