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Organ Dysfunction (organ + dysfunction)
Kinds of Organ Dysfunction Terms modified by Organ Dysfunction Selected AbstractsFluid therapy and the use of albumin in the treatment of severe traumatic brain injuryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2009M. RODLING WAHLSTRÖM Background: Evidence-based guidelines for severe traumatic brain injury (TBI) do not include strategies for fluid administration. The protocol used in this study includes albumin administration to maintain normal colloid osmotic pressure and advocates a neutral to slightly negative fluid balance. The aim of this study was to analyze the occurrence of organ failure and the mortality in patients with severe TBI treated by a protocol that includes defined strategies for fluid therapy. Methods: Ninety-three patients with severe TBI and Glasgow Coma Score,8 were included during 1998,2001. Medical records of the first 10 days were retrieved. Organ dysfunction was evaluated with the Sequential Organ Failure Assessment (SOFA) score. Mortality was assessed after 10 and 28 days, 6 and 18 months. Results: The total fluid balance was positive on days 1,3, and negative on days 4,10. The crystalloid balance was negative from day 2. The mean serum albumin was 38±6 g/l. Colloids constituted 40,60% of the total fluids given per day. Furosemide was administered to 94% of all patients. Severe organ failure defined as SOFA,3 was evident only for respiratory failure, which was observed in 29%. None developed renal failure. After 28 days, mortality was 11% and, after 18 months, it was 14%. Conclusions: A protocol including albumin administration in combination with a neutral to a slightly negative fluid balance was associated with low mortality in patients with severe TBI in spite of a relatively high frequency (29%) of respiratory failure, assessed with the SOFA score. [source] Reduced intensity allogeneic stem cell transplantation for systemic primary amyloidosis refractory to high-dose melphalanEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2004Yasukazu Kawai Abstract: Complete elimination of the plasma cell dyscrasia is a rational therapeutic goal, as intercepting supply of precursor protein is a necessary condition for a major regression of amyloid deposits. High-dose melphalan with autologous stem cell transplantation has shown the ability to induce complete hematological response (HR) along with recovery of organ dysfunction. However, the rate of HR with this treatment rarely exceeds 40%. We describe here the first known case of successful reduced intensity allogeneic stem cell transplantation (RIST) for a patient with primary amyloidosis complicated with nephrotic syndrome but without cardiac disease, who had obtained only partial HR by high-dose melphalan with autologous stem cell transplantation. RIST may be feasible and be capable of achieving complete HR along with recovery from nephrotic syndrome with acceptable toxicity. [source] Adrenal Insufficiency in Critically Ill Emergency Department Patients: A Taiwan Preliminary StudyACADEMIC EMERGENCY MEDICINE, Issue 7 2001Shy-Shin Chang MD Objective: Unrecognized adrenal insufficiency can have serious consequences in critically ill emergency department (ED) patients. This prospective pilot study of adrenal function in patients with severe illness was undertaken to determine the prevalence of adrenal dysfunction and any relation to prior herbal drug use. Methods: In a high-volume urban tertiary care ED, adult patients with sepsis or acute myocardial infarction (AMI) were eligible for the study. Over a two-month period, a convenience sample was enrolled by the authors on arrival to the ED. Inclusion criteria were systemic inflammatory response syndrome (SIRS) criteria plus evidence of at least one organ dysfunction or cardiac marker plus electrocardiogram-proven AMI. Exclusion criteria included known corticosteroid use. Serum cortisol was measured on arrival and for those patients with a level of <15 ,g/dL (<414 nmol/L), an adrenocorticotropic hormone (ACTH) stimulation test was performed. Results: Of the 30 enrolled patients, 23 (77%) were suffering from severe sepsis and the other seven (23%) had an AMI. Thirteen of the 30 patients (43%; 95% CI = 25% to 65%) had serum cortisol levels of <15 ,g/dL, consistent with adrenal insufficiency, nine with severe sepsis and four with an AMI. Eight (62%; 95% CI = 32% to 86%) of the 13 patients with low cortisol levels reported using herbal medications, while only two (12%; 95% CI = 1% to 36%) of the 17 with normal cortisol levels reported taking herb drugs (p = 0.01). Only two (15%; 95% CI = 2% to 45%) of the patients with low cortisol levels failed their corticotropin stimulation test, suggestive of true adrenocortical insufficiency. Both reported using herbal preparations. Conclusions: These results indicate that adrenal dysfunction is common among a group of critically ill patients seen in this Taiwanese ED. Moreover, the use of herbal drugs was high in the patients with low serum cortisols. Further studies are required to both confirm these findings and clarify whether a number of herbal medications contain corticosteroids. [source] Present status and perspectives regarding the therapeutic strategy for acute myeloid leukemia, non-Hodgkin's lymphoma and multiple myeloma in the elderlyGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2 2009Masatsugu Ohta The incidence of cancers increases with advancing age. To improve the quality of life of elderly patients with hematological malignancies, appropriate therapeutic approaches have to be provided under adequate informed consent and with evaluation of the prognostic factors that predict the therapeutic outcome of each disease. Even in elderly patients, combination chemotherapies are effective for obtaining a good outcome for selected populations judged by factors such as performance status, pre-existing comorbid conditions or disease features; however, non-intensive treatment or supportive care might also be considered for patient groups with a poor prognosis. Therefore, the clinical parameters of the relevance for treatment decisions in the elderly are herein addressed. During cancer treatment, attention must be paid to the presence of age-related organ dysfunction, drug resistance, drug-induced side-effects such as end organ-targeted toxicity, or neutropenia due to myelosuppression by cytotoxic drugs. Current therapeutic approaches are therefore expected to have good compliance and better outcome in elderly patients by the introduction of several molecularly targeted therapies, novel nucleoside analogs or non-myeloablative stem cell transplantation. [source] Current status of minimally invasive necrosectomy for post-inflammatory pancreatic necrosisHPB, Issue 2 2009Benoy Idicula Babu Abstract Objective:, This paper reviews current knowledge on minimally invasive pancreatic necrosectomy. Background:, Blunt (non-anatomical) debridement of necrotic tissue at laparotomy is the standard method of treatment of infected post-inflammatory pancreatic necrosis. Recognition that laparotomy may add to morbidity by increasing postoperative organ dysfunction has led to the development of alternative, minimally invasive methods for debridement. This study reports the status of minimally invasive necrosectomy by different approaches. Methods:, Searches of MEDLINE and EMBASE for the period 1996,2008 were undertaken. Only studies with original data and information on outcome were included. This produced a final population of 28 studies reporting on 344 patients undergoing minimally invasive necrosectomy, with a median (range) number of patients per study of nine (1,53). Procedures were categorized as retroperitoneal, endoscopic or laparoscopic. Results:, A total of 141 patients underwent retroperitoneal necrosectomy, of whom 58 (41%) had complications and 18 (13%) required laparotomy. There were 22 (16%) deaths. Overall, 157 patients underwent endoscopic necrosectomy; major complications were reported in 31 (20%) and death in seven (5%). Laparoscopic necrosectomy was carried out in 46 patients, of whom five (11%) required laparotomy and three (7%) died. Conclusions:, Minimally invasive necrosectomy is technically feasible and a body of evidence now suggests that acceptable outcomes can be achieved. There are no comparisons of results, either with open surgery or among different minimally invasive techniques. [source] Nonalcoholic fatty pancreas diseaseHPB, Issue 4 2007Abhishek Mathur Abstract Background. Obesity leads to fat infiltration of multiple organs including the heart, kidneys, and liver. Under conditions of oxidative stress, fat-derived cytokines are released locally and result in an inflammatory process and organ dysfunction. In the liver, fat infiltration has been termed nonalcoholic fatty liver disease, which may lead to nonalcoholic steatohepatitis. No data are available, however, on the influence of obesity on pancreatic fat and cytokines, and nonalcoholic fatty pancreas disease (NAFPD) has not been described. Therefore, we designed a study to determine whether obesity is associated with increased pancreatic fat and cytokines. Materials and methods. Thirty C57BL/6J lean control and 30 leptin-deficient obese female mice were fed a 15% fat diet for 4 weeks. At 12 weeks of age all animals underwent total pancreatectomy. Pancreata from each strain were pooled for measurement of a) wet and dry weight, b) histologic presence of fat, c) triglycerides, free fatty acids (FFAs), cholesterol, phospholipids, and total fat, and d) interleukin (IL)-1, and tumor necrosis factor-alpha (TNF-,). Data were analyzed by Student's t test and Fisher's exact test. Results. Pancreata from obese mice were heavier (p<0.05) and had more fat histologically (p<0.05). Pancreata from obese mice had more triglycerides, FFAs, cholesterol, and total fat (p<0.05). Triglycerides represented 11% of pancreatic fat in lean mice compared with 67% of pancreatic fat in obese mice (p<0.01). Cytokines IL-1, and TNF-, also were elevated in the pancreata of obese mice (p<0.05). Conclusions. These data suggest that obese mice have 1) heavier pancreata, 2) more pancreatic fat, especially triglycerides and FFAs, and 3) increased cytokines. We conclude that obesity leads to nonalcoholic fatty pancreatic disease. [source] Hyperbaric oxygen therapy and liver transplantationHPB, Issue 3 2007VIJAYARAGAVAN MURALIDHARAN Abstract Liver transplantation is the treatment of choice for end stage liver disease and is often used for primary liver malignancies. The main limitation of its wider application is the availability of suitable donor organs. The use of marginal donor organs, split-liver transplantation and living-related liver transplantation techniques contribute to increase the donor pool. However, the use of these techniques is associated with a higher risk of post transplantation organ dysfunction, predominantly due to ischaemia, preservation and reperfusion injury (IPRI). A number of studies have demonstrated that hyperbaric oxygen (HBO) therapy influences IPRI and consequential acute cellular rejection. This article reviews the rationale of HBO therapy in the field of transplantation with particular emphasis on liver transplantation. [source] Gene response elements, genetic polymorphisms and epigenetics influence the human dietary requirement for cholineIUBMB LIFE, Issue 6 2007Steven H. Zeisel Abstract Recent progress in the understanding of the human dietary requirement for choline highlights the importance of genetic variation and epigenetics in human nutrient requirements. Choline is a major dietary source of methyl-groups (one of choline's metabolites, betaine, participates in the methylation of homocysteine to form methionine); also choline is needed for the biosynthesis of cell membranes, bioactive phospholipids and the neurotransmitter acetylcholine. A recommended dietary intake for choline in humans was set in 1998, and a portion of the choline requirement can be met via endogenous de novo synthesis of phosphatidylcholine catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT) in the liver. Though many foods contain choline, many humans do not get enough in their diets. When deprived of dietary choline, most adult men and postmenopausal women developed signs of organ dysfunction (fatty liver, liver or muscle cell damage, and reduces the capacity to handle a methionine load, resulting in elevated homocysteine). However, only a portion of premenopausal women developed such problems. The difference in requirement occurs because estrogen induces expression of the PEMT gene and allows premenopausal women to make more of their needed choline endogenously. In addition, there is significant variation in the dietary requirement for choline that can be explained by common polymorphisms in genes of choline and folate metabolism. Choline is critical during fetal development, when it alters DNA methylation and thereby influences neural precursor cell proliferation and apoptosis. This results in long term alterations in brain structure and function, specifically memory function. IUBMB Life, 59: 380 - 387, 2007 [source] Toxicogenomics: a pivotal piece in the puzzle of toxicological researchJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2007Elisavet T. Gatzidou Abstract Toxicogenomics, resulting from the merge of conventional toxicology with functional genomics, being the scientific field studying the complex interactions between the cellular genome, toxic agents in the environment, organ dysfunction and disease state. When an organism is exposed to a toxic agent the cells respond by altering the pattern of gene expression. Genes are transcribed into mRNA, which in turn is translated into proteins that serve in a variety of cellular functions. Toxicogenomics through microarray technology, offers large-scale detection and quantification of mRNA transcripts, related to alterations in mRNA stability or gene regulation. This may prove advantageous in toxicological research. In the present review, the applications of toxicogenomics, especially to mechanistic and predictive toxicology are reported. The limitations arising from the use of this technology are also discussed. Additionally, a brief report of other approaches, using other -omic technologies (proteomics and metabonomics) that overcome limitations and give global information related to toxicity, is included. Copyright © 2007 John Wiley & Sons, Ltd. [source] Side Effects of Cardiopulmonary Bypass:JOURNAL OF CARDIAC SURGERY, Issue 6 2004What Is the Reality? This is due, in part, to lack of suitable control group against which bypass and cardioplegic arrest can be compared. The recent success of beating heart coronary artery bypass grafting has, however, for the first time, provided an opportunity to compare the same operation, in similar patient groups, with, or without CPB and cardioplegic arrest. CPB is associated with an acute phase reaction of protease cascades, leucocyte, and platelet activation that result in tissue injury. This is largely manifest as subclinical organ dysfunction that produces a clinical effect in those patients that generate an excessive inflammatory response or in those with limited functional reserve. The contribution of myocardial ischemia/reperfusion, secondary to aortic cross-clamping, and cardioplegic arrest, to the systemic inflammatory response and wider organ dysfunction is unknown, and requires further evaluation in clinical trials. [source] Isoflurane attenuates pulmonary interleukin-1, and systemic tumor necrosis factor-, following mechanical ventilation in healthy miceACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2009M. VANEKER Background: Mechanical ventilation (MV) induces an inflammatory response in healthy lungs. The resulting pro-inflammatory state is a risk factor for ventilator-induced lung injury and peripheral organ dysfunction. Isoflurane is known to have protective immunological effects on different organ systems. We tested the hypothesis that the MV-induced inflammatory response in healthy lungs is reduced by isoflurane. Methods: Healthy C57BL6 mice (n=34) were mechanically ventilated (tidal volume, 8 ml/kg; positive end-expiratory pressure, 4 cmH2O; and fraction of inspired oxygen, 0.4) for 4 h under general anesthesia using a mix of ketamine, medetomidine and atropine (KMA). Animals were divided into four groups: (1) Unventilated control group; (2) MV group using KMA anesthesia; (3) MV group using KMA with 0.25 MAC isoflurane; (4) MV group using KMA with 0.75 MAC isoflurane. Cytokine levels were measured in lung homogenate and plasma. Leukocytes were counted in lung tissue. Results: Lung homogenates: MV increased pro-inflammatory cytokines. In mice receiving KMA+ isoflurane 0.75 MAC, no significant increase in interleukin (IL)-1, was found compared with non-ventilated control mice. Plasma: MV induced a systemic pro-inflammatory response. In mice anesthetized with KMA+ isoflurane (both 0.25 and 0.75 MAC), no significant increase in tumor necrosis factor (TNF)-, was found compared with non-ventilated control mice. Conclusions: The present study is the first to show that isoflurane attenuates the pulmonary IL-1, and systemic TNF-, response following MV in healthy mice. [source] Evodia rutaecarpa protects against circulation failure and organ dysfunction in endotoxaemic rats through modulating nitric oxide releaseJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2002Wen Fei Chiou Using a rat model of septic shock we studied the effects of Evodia rutaecarpa, a Chinese herbal medicine with antimicrobial and anti-inflammatory activity, on haemodynamic parameters, biochemical markers of organ function and nitric oxide (NO) production. Anaesthetized rats challenged with a high dosage of endotoxin (Escherichia coli lipopolysaccharide; LPS; 50 mg kg,1, i.v.) for 6 h showed a severe decrease in mean arterial pressure. This was accompanied by delayed bradycardia, vascular hyporeactivity to phenylephrine and increase in plasma levels of lactate dehydrogenase, aspartate aminotransferase, bilirubin and creatinine, as well as NOx (NO,2 plus NO,3). Pretreatment with ethanol extract of E. rutaecarpa (25,50 and 100 mg kg,1, i.v.), 1 h before LPS, dose-dependently prevented the circulation failure, vascular hyporeactivity to phenylephrine, prevented liver dysfunction and reduced the NOx over-production in plasma in endotoxaemic rats. A selective inducible NO-synthase (iNOS) inhibitor, aminoguanidine (15 mg kg,1, i.v.), also effectively ameliorated the above pathophysiological phenomenon associated with endotoxaemia so that the normal condition was approached. Endotoxaemia for 6 h resulted in a significant increase in iNOS activity in the liver homogenate, which was attenuated significantly by E. rutaecarpa pretreatment. In summary, E. rutaecarpa, at the dosages used, exerted these beneficial effects probably through inhibition of iNOS activity and subsequent modulation of the release of NO. These significant results may offer E. rutaecarpa as a candidate for the treatment of this model of endotoxaemia. [source] Development of renal failure during the initial 24 h of intensive care unit stay correlates with hospital mortality in trauma patientsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2006T. Ala-Kokko Background:, Although multiple organ failure is the leading late cause of death, there is controversy about the impact of acute organ dysfunction and failure on trauma survival. Methods:, Consecutive adult trauma admissions between January 2000 and June 2003, excluding isolated head traumas and burns, were analysed for parameters of organ function during the first 24 h following intensive care unit (ICU) admission using the Sequential Organ Failure Assessment (SOFA) scoring system. A national prospectively collected ICU data registry was used for analysis, including data from 22 ICUs in university and central hospitals in Finland. Results:, The study population consisted of 1044 eligible trauma admissions; 32% of the cases were treated at university hospital level, the rest being secondary referral central hospital admissions. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 15 (SD8), ICU mortality was 5.6% and a further 1.6% of patients died during their post-ICU hospital stay. Forty-five per cent of the patients were categorized as having multiple traumas. In univariate analysis, APACHE II , 25 [odds ratio (OR), 35; 95% confidence interval (CI), 18,66] and renal failure (OR, 29.5; 95% CI, 14,63) produced the highest ORs for ICU mortality. In the APACHE II-, sex- and age-adjusted logistic regression model, renal failure was a significant risk factor for both ICU and hospital mortality (OR, 11.8; 95% CI, 3.9,35.4; OR, 8.2; 95% CI, 2.9,23.2, respectively). Conclusion:, The development of renal failure during the initial 24 h of ICU stay remained an independent risk factor for mortality in trauma patients requiring intensive care treatment even after adjusting for the APACHE II score, age and sex. [source] ADAMTS-13, von Willebrand factor and related parameters in severe sepsis and septic shockJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2007J. A. KREMER HOVINGA Summary. Background:,Insufficient control of von Willebrand factor (VWF) multimer size as a result of severely deficient ADAMTS-13 activity results in thrombotic thrombocytopenic purpura associated with microvascluar thrombosis and platelet consumption, features not seldom seen in severe sepsis and septic shock. Methods:,ADAMTS-13 activity and VWF parameters of 40 patients with severe sepsis or septic shock were compared with those of 40 healthy controls of the same age and gender and correlated with clinical findings and sepsis outcome. Results:,ADAMTS-13 activity was significantly lower in patients than in healthy controls [median 60% (range 27,160%) vs. 110% (range 63,200%); P < 0.001]. VWF parameters behaved reciprocally and both VWF ristocetin cofactor activity (RCo) and VWF antigen (VWF:Ag) were significantly (P < 0.001) higher in patients compared with controls. Neither ADAMTS-13 activity nor VWF parameters correlated with disease severity, organ dysfunction or outcome. However, a contribution of acute endothelial dysfunction to renal impairment in sepsis is suggested by the significantly higher VWF propeptide and soluble thrombomodulin levels in patients with increased creatinine values as well as by their strong positive correlations (creatinine and VWF propeptide rs = 0.484, P < 0.001; creatinine and soluble thrombomodulin rs = 0.596, P < 0.001). Conclusions:,VWF parameters are reciprocally correlated with ADAMTS-13 activity in severe sepsis and septic shock but have no prognostic value regarding outcome. [source] BIOCHEMICAL MARKERS OF CARDIAC INJURY IN NORMAL AND SURVIVING VERSUS NON-SURVIVING SEPTICEMIC NEONATAL FOALSJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue S1 2004SF Peek Although myocardial injury can be a significant component of multiple organ dysfunction (MODS) in association with septicemia in critically ill human patients, it is as yet an undefined clinical entity in equine septicemia. With septicemia as the leading cause of death in neonatal foals, a better understanding of the pathophysiology, diagnosis and treatment of MODS will be important in further improving survival rates. We designed a prospective study to establish normal ranges for cardiac troponin I (cTnI), T (cTnT) and CKMB mass in healthy 24,48 hour old foals, as well as septicemic neonatal foals seen over a 2-year period in a teaching hospital. We also performed a comparison of these biomarkers in surviving and non-surviving septicemic foals. Sepsis was judged on the basis of the presence of any of the 3 following criteria: blood culture positive at admission, admission sepsis score ,11, or 3 or more sites of infection during hospitalization in foals ,14 days of age. cTnI was measured by the ACCESS® (Beckman Coulter), cTnT was measured using the Elecsys 2010® Immunoassay (Roche), and CKMB mass measurements were performed using the Elecsys 2010®. Each parameter was described using range and 95th and 50th percentile. Comparisons were made for each parameter between normal and septic foals as well as surviving and non-surviving septic foals using the non-parametric Wilcoxon's rank sum test. Significance was set at p<0.05. There were 52 control foals and 38 septic foals of which 22 survived. Significant differences were documented for CKMB between septicemic and normal foals, but not for cTnT or cTnI. However, CKMB and cTnT were significantly lower in surviving versus non-surviving septicemic foals. The 50th and 95th percentiles alongside the ranges for the normal foal population were 0.14, 0.49, (0.01,0.51) ,g/L for cTnI, 0.009, 0.03, (0.009,0.04) ,g/L for cTnT and 2.3, 7.4, (0.4,9.3) ,g/L for CKMB. Our findings suggest that myocardial injury is a component of MODS during septicemia in foals, and that quantitatively significant increases in CKMB and cTnT are seen in non-surviving septicemic foals versus survivors. [source] Critical role of the vascular endothelial cell in health and disease: a review articleJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2004Todd C. Duffy DVM Abstract Objective: To review the human and veterinary literature on the role of the vascular endothelial cell in health, as well as during hypoxic and inflammatory disease states. Data sources: Data from human and veterinary literature were reviewed through a Pubmed search and a manual search of the references listed in articles covering some aspect of vascular endothelial cell function. Human data synthesis: The development of techniques that allow the maintenance and growth of endothelial cells in culture has produced an explosion of new research in the area of endothelial cell physiology. This plethora of data has revealed the critical role that vascular endothelial cells play in both health and disease states. Interspecies variations can occur with respect to the vascular endothelial cell physiology and its response to pathologic conditions. Veterinary data synthesis: There is a paucity of information regarding the role of the vascular endothelial cell in health or disease of small animals. Many human studies use species cared for by veterinarians, providing information that may be applied to small animals and that may be used to construct future studies. Conclusion: An organ system itself, the vascular endothelium is an essential component of all organs in the body. The endothelial cell lining functions to maintain selective permeability between the blood and the tissue it supplies, regulate vascular tone, sustain blood fluidity through regulation of coagulation, and modulate interaction of leukocytes with the interstitium and inflammatory reactions. During disease states, the endothelial cell functions locally to limit the boundaries of the disease process. If these functions are not controlled, they can become a part of the pathogenic process, contributing to blood stasis and thrombosis, potentiation of local inflammation and interstitial edema formation, subsequent tissue hypoxia, and multiple organ dysfunction. Pharmacological investigations targeting the modulation of endothelial function during disease states have not yet advanced treatment protocols. Since all critically ill animals are at risk for some degree of endothelial cell dysfunction, treatment regimens should focus on promoting capillary blood flow and tissue oxygen delivery. [source] Use of activated protein c in liver transplantation patients with septic shock,LIVER TRANSPLANTATION, Issue 11 2008Laura Rinaldi Recombinant human activated protein C (rhAPC) has been approved for use in patients with severe sepsis at high risk of death. Because of the high risk of bleeding, liver transplantation (LT) patients have been excluded from the randomized control trials that evaluated efficacy and safety of rhAPC and, thus, few data are available on the use of this drug in LT patients with severe sepsis. We describe our experience with 5 LT recipients treated for septic shock with the best conventional therapy and rhAPC. Before rhAPC therapy, all the patients showed septic shock, with ,3 organ dysfunctions and thrombocytopenia with impairment of coagulation. rhAPC therapy started within 30 hours after septic shock onset in all the patients who recovered from sepsis-induced circulatory failure, improved organ dysfunction, and completed the 96 hours of rhAPC therapy. During rhAPC infusion, 4 patients received fresh frozen plasma and/or platelet concentrates because of thrombocytopenia and severe hemostasis dysfunction. No major bleeding occurred and only 1 patient presented with minor bleeding events. Liver Transpl 14:1598,1602, 2008. © 2008 AASLD. [source] Influence of extracorporeal porcine liver perfusion on nonhuman primates: Minimizing hemolysis improves subsequent survivalLIVER TRANSPLANTATION, Issue 7 2001Ryuta Nishitai MD The aim of this study is to detect and analyze risk factors of direct cross-circulation between porcine liver and nonhuman primates before a clinical application of extracorporeal liver perfusion (ECLP) as a liver-assist method. Porcine livers were perfused with baboon blood in an ECLP system. Six healthy baboons were directly connected to the ECLP system with continuous prostaglandin E1 administration. Cross-circulation was terminated in the following circumstances: (1) hepatic arterial or portal perfusion pressures elevated to 200 or 60 mm Hg, respectively; (2) massive exudative bleeding from the graft surface; or (3) bile output decreased to less than 5 ,L/h/g of liver weight. In case 1, cross-circulation was continued for 10 hours. Severe macroscopic hemolysis occurred, and serum hemoglobin (s-Hb) concentration reached a peak of 47 mg/dL. The baboon died of acute renal failure 2 days later. Histological study of the perfused porcine liver showed marked microthrombi formation. In 3 of the later 5 cases, cross-circulation was discontinued when mild macroscopic hemolysis was observed. The duration of the 5 cross-circulations was maximally 6 hours (mean, 4.4 ± 1.2 [SD] hours). Mean s-Hb concentration in the 5 cases was elevated to 14.8 ± 5.8 mg/dL at the end of cross-circulation and decreased to the baseline level within 24 hours. These 5 baboons survived without organ dysfunction or immunologic disturbance. When severe hemolysis is avoided, direct cross-circulation using the ECLP system can be achieved without serious complications in nonhuman primates. [source] The Pancreas as a Source of Cardiovascular Cell Activating FactorsMICROCIRCULATION, Issue 3 2000ERIK B. KISTLER ABSTRACT Objective: Physiological shock leads to elevated levels of plasma factors that activate circulating leukocytes and endothelial cells, thereby compromising microvascular functions. The nature and source of these plasma-derived activators are unknown. To examine the possible origin of these factors, we homogenized rat internal organs and measured their activity on cardiovascular cells in vivo and in vitro. Methods: Fresh tissue samples from small intestine, spleen, heart, liver, kidney, adrenals, and pancreas were homogenized. Their ability to induce leukocyte pseudopod formation and nitroblue tetrazolium (NBT) reduction was tested and their impact in vivo on blood pressure, survival, and microvascular cell injury was examined. Results: A dramatic increase (p < 0.001) in leukocyte activation compared to controls was observed with pancreas homogenate but not with homogenates from the other organs. Leukocyte activation was induced by homogenates of other tissues only after prior incubation with substimulatory concentrations of pancreatic homogenate. Pancreatic serine proteases, trypsin and chymotrypsin, which did not stimulate leukocytes, also generated activity from other tissues. Leukocyte pseudopod formation could be significantly inhibited by adding the serine protease inhibitor 6-amidino-2-naphthyl p -guanidinobenzoate dimethanesulfonate (ANGD) during tissue homogenization (p < 0.001). Injection of pancreatic homogenate into rats led to increased plasma hydrogen peroxide levels and an instantaneous drop in mean arterial pressure that was often lethal. These responses were prevented by prior infusion of ANGD (p < 0.001). Intravital microscopy of the rat mesentery confirmed that superfusion of filtered pancreatic homogenate leads to significant increases in cell death (p < 0.05), as detected by propidium iodide, and hydrogen peroxide formation (p < 0.05), as determined by dichlorofluorescein diacetate (DCFH) fluorescence. Conclusion: These results suggest that pancreatic enzymes attack tissue and generate cellular activators that are associated with organ dysfunction in shock. [source] Temperature-related fluid extravasation during cardiopulmonary bypass: An analysis of filtration coefficients and transcapillary pressuresACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2002J. K. Heltne Background: Cardiopulmonary bypass (CPB) as used for cardiac surgery and for rewarming individuals suffering deep accidental hypothermia is held responsible for changes in microvascular fluid exchange often leading to edema and organ dysfunction. The purpose of this work is to improve our understanding of fluid pathophysiology and to explore the implications of the changes in determinants of transcapillary fluid exchange during CPB with and without hypothermia. This investigation might give indications on where to focus attention to reduce fluid extravasation during CPB. Methods: Published data on "Starling variables" as well as reported changes in fluid extravasation, tissue fluid contents and lymph flow were analyzed together with assumed/estimated values for variables not measured. The analysis was based on the Starling hypothesis where the transcapillary fluid filtration rate is given by: JV=Kf[Pc,Pi,,(COPp,COPi)]. Here Kf is the capillary filtration coefficient, , the reflection coefficient, P and COP are hydrostatic and colloid osmotic pressures, and subscript ,c' refers to capillary, ,i` to the interstitium and `p' to plasma. Results and conclusion: The analysis indicates that attempts to limit fluid extravasation during normothermic CPB should address primarily changes in Kf, while changes in both Kf and Pc must be considered during hypothermic CPB. [source] The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up,,§¶,,,,,§§AMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2010Martin H. Steinberg A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at , = 0.05 level (P -value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc. [source] Urgent liver transplantation for Amanita phalloides poisoningPEDIATRIC TRANSPLANTATION, Issue 1 2008Baris Dogu Yildiz Abstract:,Amanita phalloides is a deadly wild mushroom causing severe damage in man ranging from diarrhea to organ dysfunction. If not treated, mortality is as high as 80%. Treatment includes supportive measures, inactivation of the toxin and if liver failure occurs liver transplantation. The indications for transplantation are debatable. [source] Reduced-intensity allogeneic hematopoietic cell transplantation: Graft versus tumor effects with decreased toxicityPEDIATRIC TRANSPLANTATION, Issue 3 2003Jennifer E. Schwartz Abstract: The potentially curative role of allogeneic hematopoietic cell transplantation (HCT) in neoplastic and non-neoplastic diseases is offset by the substantial risks of morbidity and mortality from complications of the intensive myeloablative and immunosuppressive preparative regimen. These regimen-related toxicities have restricted allogeneic HCT to young, otherwise healthy individuals without comorbid diseases. Pediatric patients undergoing conventional allogeneic HCT have lower procedure-related mortality but are at risk for non-fatal late effects of the high-dose pretransplant chemoradiotherapy, such as growth retardation, sterility and other endocrine dysfunction. Evaluation of reduced-intensity preparative regimens is the major focus of current clinical research in allogeneic HCT. Reduced-intensity HCT (RI-HCT) relies on the use of immunosuppressive but non-myeloablative agents that allow engraftment of donor cells, which provide adoptive allogeneic cellular immunotherapy and graft versus tumor (GVT) effects, with decreased regimen-related toxicities. Although the experience with RI-HCT in pediatric patients is very limited at this time, results in adults indicate that attenuated-dose preparative regimens allow older patients and those with organ dysfunction to undergo successful allogeneic HCT with acceptable morbidity and mortality. In adults, the potency of the allogeneic GVT effect varies among neoplastic diseases, with better results observed in patients with indolent hematological malignancies or renal cell carcinoma. The effectiveness of RI-HCT as treatment for children with hemoglobinopathies, chronic granulomatous disease and cellular immunodeficiencies is encouraging, and the role of reduced-intensity preparative regimens for allogeneic HCT in pediatric malignancies is under investigation. [source] Case Report: Extracorporeal Membrane Oxygenation in Nonintubated Patients as Bridge to Lung TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010K. M. Olsson We report on the use of veno-arterial extracorporeal membrane oxygenation (ECMO) as a bridging strategy to lung transplantation in awake and spontaneously breathing patients. All five patients described in this series presented with cardiopulmonary failure due to pulmonary hypertension with or without concomitant lung disease. ECMO insertion was performed under local anesthesia without sedation and resulted in immediate stabilization of hemodynamics and gas exchange as well as recovery from secondary organ dysfunction. Two patients later required endotracheal intubation because of bleeding complications and both of them eventually died. The other three patients remained awake on ECMO support for 18,35 days until the time of transplantation. These patients were able to breathe spontaneously, to eat and drink, and they received passive and active physiotherapy as well as psychological support. All of them made a full recovery after transplantation, which demonstrates the feasibility of using ECMO support in nonintubated patients with cardiopulmonary failure as a bridging strategy to lung transplantation. [source] Progression of Organ Failure in Patients Approaching Brain Stem DeathAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009F. T. Lytle We performed a retrospective cohort study to document the progression of organ dysfunction in 182 critically ill adult patients who subsequently met criteria for brain stem death (BSD). Patients were admitted to intensive care units (ICUs) of Mayo Medical Center, Rochester, MN, between January 1996 and December 2006. Daily sequential organ failure assessment (SOFA) scores were used to assess the degree of organ dysfunction. Serial SOFA scores were analyzed using analysis of variance (ANOVA). Mean (standard deviation, SD) SOFA score on the first ICU day was 8.9 (3.2). SOFA scores did not significantly change over the course of ICU stay. 67.6% of patients donated one or more organs after BSD was declared. The median time from ICU admission to declaration of BSD was 18.8 h (interquartile range 10.3,45.0), and in those who donated organs, the time from declaration of BSD to organ retrieval was 11.8 h (9.5,17.6). The fact that mean SOFA scores did not change significantly over time, even after BSD occurred, has implications for the timing of retrieval of organs for transplantation. [source] Successful Long-Term Outcome of the First Combined Heart and Kidney Transplant in a Patient with Systemic AL AmyloidosisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009V. Audard Simultaneous cardiac and renal involvement is associated with a particularly poor prognosis in patients with AL amyloidosis (AL-A). We report the first case of a successful long-term outcome of combined heart and kidney transplantation not followed by autologous stem cell transplantation in a patient with systemic AL-A. The recipient was a 46-year-old man with end-stage renal failure associated with serious cardiac involvement in the context of AL-A. Before transplantation, two courses of oral melphalan plus prednisone induced partial hematologic remission, as shown by the decrease in circulating free light chain with no improvement of renal or heart function. The patient underwent combined heart and kidney transplantation as a rescue treatment. During the follow-up period (36 months), plasma cell dyscrasia remains in complete remission, with normal free lambda light chain levels and no recurrence of amyloid deposition on heart and kidney grafts. This case report demonstrates that combined heart and kidney transplantation not systematically associated with stem cell transplantation may be considered an additional therapeutic option in AL-A patients with severe organ dysfunction and partial hematologic remission. [source] Systemic complications after head injury: a clinical reviewANAESTHESIA, Issue 5 2007H. B. Lim Summary Non-neurological organ dysfunction is common after traumatic brain injury and is an independent contributor to morbidity and mortality. It represents a risk factor that is potentially amenable to treatment, and early recognition and prompt intervention may improve outcome. This article reviews the current evidence for the mechanisms and treatment of non-neurological organ dysfunction after head injury. [source] Independent association of anti,,2 -glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patientsARTHRITIS & RHEUMATISM, Issue 8 2009Francesco Boin Objective Systemic sclerosis (SSc; scleroderma) is characterized by a unique widespread vascular involvement that can lead to severe digital ischemia, pulmonary arterial hypertension (PAH), or other organ dysfunction. Microthrombotic events and procoagulation factors such as anti,,2-glycoprotein I (anti-,2GPI) or anticardiolipin antibodies (aCL) may be implicated in the development of these manifestations. This study was undertaken to investigate whether anti-,2GPI and aCL are correlated with macrovascular disease, including ischemic digital loss and PAH, in SSc patients. Methods Seventy-five SSc patients with a history of ischemic digital loss and 75 matched SSc controls were evaluated. Anticentromere antibodies (ACAs), anti-,2GPI, and aCL were measured, and clinical associations were determined using conditional and simple logistic regression models. Results Positivity for anti-,2GPI was significantly more frequent in SSc patients with digital loss than in patients without digital loss (P = 0.017), with the IgA isotype of anti-,2GPI showing the strongest association (odds ratio [OR] 4.0). There was no significant difference in aCL frequency between patients with digital loss and control patients. After adjustment for demographic characteristics, disease type, smoking, and ACA, anti-,2GPI positivity was significantly associated with active digital ischemia (OR 9.4), echocardiographically evident PAH (OR 4.8), and mortality (OR 2.9). ACA positivity was associated with history of digital loss (OR 3.28), but not with PAH or mortality. History of digital loss was strongly associated with increased mortality (OR 12.5). Conclusion Anti-,2GPI is significantly associated with macrovascular disease in SSc and independently predicts mortality. It is unclear whether it has a pathogenetic role or simply reveals the presence of underlying endothelial injury. The use of anti-,2GPI as a biomarker of vascular disease in SSc should be further explored. [source] Ductular Cholestasis, an Unusual Form of Intrahepatic Cholestasis, Associated With Cardiogenic Shock and Ventricular Assist DeviceARTIFICIAL ORGANS, Issue 2 2010Alberto Mohedano-Gómez Abstract Ventricular assist devices have been shown to be effective in advanced heart failure selected patients. They often have borderline end-organ function, what facilitates organ dysfunction. Liver failure is difficult to manage and leads to increased morbidity and mortality. We report a case of ductular cholestasis, an unusual cholestatic hepatic failure with untractable coagulopathy, developed during the use of a magnetic levitation centrifugal pump, implanted as a bridge to heart transplantation, in a patient with cardiogenic shock (as an end-stage disease of idiopathic dilated cardiomyopathy). We discussed the pathophysiology of this entity and the possible related factors, including the assist device. Preemptive interventions have been advocated as the primary way of treatment. Preoperative optimization of heart function and avoidance of visceral hypoperfusion and sepsis may play a major role. [source] Activation of Neutrophil Granulocytes in an In Vitro Model of a Cardiopulmonary BypassARTIFICIAL ORGANS, Issue 12 2005Ann Elisabeth Åsberg Abstract: Activated neutrophils play a central role in the pathogenesis of postoperative organ dysfunction after surgery with cardiopulmonary bypass. The researchers used an in vitro roller pump model to investigate the relative importance of the biomaterial, platelets, plasma proteins including activated complement, and flow mode on neutrophil activation as shown by the adhesion, degranulation, and increased the surface expression of CD11b. Neutrophil adhesion to the biomaterial increased with platelet addition, but not with plasma. Biomaterial contact activated neutrophils in a serum-free buffer, but was significantly increased by activated complement. Platelets increased neutrophil degranulation in a serum-free buffer but tended to reduce it in plasma. CD11b expression increased in both media. Complement activation was higher with neutrophils alone than with neutrophils and platelets combined. The roller pump reduced neutrophil adhesion and increased degranulation compared to passive rotation. Neutrophil interaction with platelets and complement were more important for activation than biomaterial contact and use of the roller pump. Improvement of biocompatibility is dependent on modifying complement activation and platelet interaction with neutrophils. [source] | |||||||||||||||||||||||||||||||||||||