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Sample records for acute organ dysfunction

  1. Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis.

    PubMed

    Gordon, Anthony C; Perkins, Gavin D; Singer, Mervyn; McAuley, Daniel F; Orme, Robert M L; Santhakumaran, Shalini; Mason, Alexina J; Cross, Mary; Al-Beidh, Farah; Best-Lane, Janis; Brealey, David; Nutt, Christopher L; McNamee, James J; Reschreiter, Henrik; Breen, Andrew; Liu, Kathleen D; Ashby, Deborah

    2016-10-27

    Background Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis. Methods We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20). Secondary outcomes included 28-day mortality, time to weaning from mechanical ventilation, and adverse events. Results The trial recruited 516 patients; 259 were assigned to receive levosimendan and 257 to receive placebo. There was no significant difference in the mean (±SD) SOFA score between the levosimendan group and the placebo group (6.68±3.96 vs. 6.06±3.89; mean difference, 0.61; 95% confidence interval [CI], -0.07 to 1.29; P=0.053). Mortality at 28 days was 34.5% in the levosimendan group and 30.9% in the placebo group (absolute difference, 3.6 percentage points; 95% CI, -4.5 to 11.7; P=0.43). Among patients requiring ventilation at baseline, those in the levosimendan group were less likely than those in the placebo group to be successfully weaned from mechanical ventilation over the period of 28 days (hazard ratio, 0.77; 95% CI, 0.60 to 0.97; P=0.03). More patients in the levosimendan group than in the placebo group had supraventricular tachyarrhythmia (3.1% vs. 0.4%; absolute difference, 2.7 percentage points; 95% CI, 0.1 to 5.3; P=0.04). Conclusions The addition of levosimendan to standard treatment in adults with sepsis was not associated with less severe organ dysfunction or lower mortality

  2. Multiple organ dysfunction syndrome.

    PubMed

    Parke, A L; Liu, P T; Parke, D V

    2003-01-01

    Multiple organ dysfunction syndrome, including acute respiratory distress syndrome (ARDS) and renal failure, is described, its clinical features outlined, its origins in tissue oxidative stress following severe infections, surgical trauma, ionizing radiation, high-dosage drugs and chemicals, severe hemorrhage, etc., are defined, and its prevention and treatment prescribed.

  3. Niacinamide abrogates the organ dysfunction and acute lung injury caused by endotoxin.

    PubMed

    Kao, Shang-Jyh; Liu, Demeral David; Su, Chain-Fa; Chen, Hsing I

    2007-09-01

    Poly (ADP-ribose) synthabse (PARS) or polymerase (PARP) is a cytotoxic enzyme causing cellular damage. Niacinamide inhibits PARS or PARP. The present experiment tests the effects of niacinamide (NCA) on organ dysfunction and acute lung injury (ALI) following lipopolysaccharide (LPS). LPS was administered to anesthetized rats and to isolated rat lungs. In anesthetized rats, LPS caused systemic hypotension and increased biochemical factors, nitrate/nitrite (NOx), methyl guanidine (MG), tumor necrosis factoralpha (TNFalpha), and interleukin-1beta (IL-1beta). In isolated lungs, LPS increased lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, and capillary permeability. The insult also increased NOx, MG, TNFalpha, and IL-1beta in lung perfusate, while decreased adenosine triphosphate (ATP) content with an increase in PARP activity in lung tissue. Pathological examination revealed pulmonary edema with inflammatory cell infiltration. These changes were abrogated by posttreatment (30 min after LPS) with NCA. Following LPS, the inducible NO synthase (iNOS) mRNA expression was increased. NCA reduced the iNOS expression. Niacinamide exerts protective effects on the organ dysfunction and ALI caused by endotoxin. The mechanisms may be mediated through the inhibition on the PARP activity, iNOS expression and the subsequent suppression of NO, free radicals, and proinflammatory cytokines with restoration of ATP.

  4. HMGB1 and Histones Play a Significant Role in Inducing Systemic Inflammation and Multiple Organ Dysfunctions in Severe Acute Pancreatitis

    PubMed Central

    Tenhunen, Jyrki; Tonnessen, Tor Inge

    2017-01-01

    Severe acute pancreatitis (SAP) starts as a local inflammation of pancreatic tissue that induces the development of multiple extrapancreatic organs dysfunction; however, the underlying mechanisms are still not clear. Ischemia-reperfusion, circulating inflammatory cytokines, and possible bile cytokines significantly contribute to gut mucosal injury and intestinal bacterial translocation (BT) during SAP. Circulating HMGB1 level is significantly increased in SAP patients and HMGB1 is an important factor that mediates (at least partly) gut BT during SAP. Gut BT plays a critical role in triggering/inducing systemic inflammation/sepsis in critical illness, and profound systemic inflammatory response syndrome (SIRS) can lead to multiple organ dysfunction syndrome (MODS) during SAP, and systemic inflammation with multiorgan dysfunction is the cause of death in experimental SAP. Therefore, HMGB1 is an important factor that links gut BT and systemic inflammation. Furthermore, HMGB1 significantly contributes to multiple organ injuries. The SAP patients also have significantly increased circulating histones and cell-free DNAs levels, which can reflect the disease severity and contribute to multiple organ injuries in SAP. Hepatic Kupffer cells (KCs) are the predominant source of circulating inflammatory cytokines in SAP, and new evidence indicates that hepatocyte is another important source of circulating HMGB1 in SAP; therefore, treating the liver injury is important in SAP. PMID:28316860

  5. Effectiveness of combining plasma exchange with continuous hemodiafiltration on acute Fatty liver of pregnancy complicated by multiple organ dysfunction.

    PubMed

    Chu, Yu-Feng; Meng, Mei; Zeng, Juan; Zhou, Hai-Yan; Jiang, Jin-Jiao; Ren, Hong-Sheng; Zhang, Ji-Cheng; Zhu, Wen-Ying; Wang, Chun-Ting

    2012-06-01

    Acute fatty liver of pregnancy (AFLP) is a rare disease of progressive hepatic insufficiency and secondary systemic complications that induce significant maternal risk. The application of combining plasma exchange (PE) and continuous hemodiafiltration (CHDF) is a novel concept for patients with AFLP. Since 2002, we have utilized the combination of PE with CHDF as adjunctive medical therapy for 11 AFLP patients with multiple organ dysfunction. Before PE and CHDF initiation, four patients had signs and symptoms of encephalopathy, four required ventilatory support, and all 11 were developing liver failure, significant renal compromise, and coagulopathy. PE combined with CHDF for patients was initiated a mean of 2 days postpartum (range, days 0-3). Daily or every other day PE combined with CHDF was undertaken on two to eight occasions for each of the 11 patients. Ten patients responded with composite clinical and laboratory improvement and were discharged to the ward, then cured and discharged from hospital; one patient died of septic shock. Average duration of hospitalization was 17 days (range, days 9-38) from time of admission to discharge; the average duration of intensive care unit was 10 days (range, days 4-23). No significant PE- and CHDF-related complications occurred. These results indicate that combing PE and CHDF in a series-parallel circuit is an effective and safe treatment for patients with severe AFLP. This finding may have important implications for the development of an effective treatment for patients with AFLP suffering multiple organ dysfunction.

  6. Multiple organ dysfunction syndrome.

    PubMed Central

    Murray, M. J.; Coursin, D. B.

    1993-01-01

    The multiple organ dysfunction syndrome (MODS), though newly described, has manifested itself in intensive care unit (ICU) patients for several decades. As the name implies, it is a syndrome in which more than one organ system fails. Failure of these multiple organ systems may or may not be related to the initial injury or disease process for which the patient was admitted to the ICU. MODS is the leading cause of morbidity and mortality in current ICU practice. While the pathophysiology of MODS is not completely known, much evidence indicates that, during the initial injury which precipitates ICU admission, a chain of events is initiated which results in activation of several endogenous metabolic pathways. These pathways release compounds which, in and of themselves, are usually cytoprotective. However, an over exuberant activation of these endogenous systems results in an inflammatory response which can lead to development of failure in distant organs. As these organs fail, they activate and propagate the systemic inflammatory response. No therapy has proven entirely efficacious at modulating this inflammatory response and the incidence and severity of MODS. In current ICU practice, treatment is focused on prevention and treating individual organ dysfunction as it develops. With increased understanding of the pathophysiology of MODS therapy will come newer modalities which inhibit or interfere with the propagation of the endogenous systemic inflammatory response. These newer therapies hold great promise and already some are undergoing clinical investigation. PMID:7825351

  7. [Multiple organ dysfunction syndrome].

    PubMed

    Cuenca Solanas, M

    1999-01-01

    Multiple organ dysfunction syndrome (MODS) is a clinical situation that has been described as a result of the rapid progress and advances that have been made in recent decades in the physiology, diagnosis, and therapeutic support of critically ill patients. In 1991, in view of the confusing terminology used to characterize processes coursing with systemic inflammatory response syndrome (SIRS), a consensus conference was held. A series of basic definitions were established and the term "multiple organ failure" was replace by MODS. In response to outside aggression, the organism tries to defend itself with two mechanisms: a non-specific humoral and cellular response called inflammation, and a specific antigenic response that modifies the genetic codes of cells of the defense system and constitutes an immunological response. At present it is thought that the inflammatory response is activated (SIRS) in response to an uncontrolled aggression, but an antiinflammatory response syndrome (ARS) exists as well. An exaggerated SIRS can lead to MODS. MODS usually debuts with pulmonary dysfunction. If the aggression persists, cardiovascular, renal, hepatic, coagulation, central nervous system, gastrointestinal metabolism, neuroendocrine and musculoskeletal failure follow. A series of causes often trigger this syndrome and certain factors favor it. Prevention of these causes and factors in fundamental for controlling the occurrence of MODS. At present, there is no clear treatment for MODS, although numerous studies designed to block the release of certain proinflammatory mediators or to neutralize antiinflammatory responses are being carried out.

  8. Clinical Evaluation of High-Volume Hemofiltration with Hemoperfusion Followed by Intermittent Hemodialysis in the Treatment of Acute Wasp Stings Complicated by Multiple Organ Dysfunction Syndrome

    PubMed Central

    Si, Xiaoyun; Li, Jingjing; Bi, Xiaohong; Wu, Lan; Wu, Xiaoyan

    2015-01-01

    Multiple organ dysfunction syndrome (MODS) is a rare complication of wasp stings. Currently, there is no standardized treatment for MODS secondary to multiple wasp stings, although blood purification techniques are often used. This study aimed to analyze our experiences of using intermittent hemodialysis (IHD) with or without high-volume hemofiltration (HVHF) for treating acute wasp stings complicated by MODS. In this retrospective study, 36 patients with wasp stings complicated by MODS received either IHD combined with hemoperfusion, or HVHF (ultrafiltration flow rate, 70 mL/kg/h) combined with hemoperfusion for 5 days followed by IHD. Clinical symptoms, blood biochemical parameters, duration of mechanical ventilation, use of vasoactive agents, duration of hospital stay and survival rate were recorded, and Acute Physiology and Chronic Health Evaluation II (APACHE II) and multiple organ dysfunction (MOD) scores estimated. Patients treated with HVHF followed by IHD appeared to exhibit a faster recovery than those receiving IHD alone, as evidenced by superior improvements in MOD (4.29±1.08 vs. 2.27±1.07) and APACHE II (7.09±2.62 vs. 4.20±1.69) scores (P < 0.05). Patients treated with HVHF had significantly lower myoglobin, creatine kinase-MB, lactate dehydrogenase, bilirubin and creatinine levels than patients treated with IHD alone. In addition, the durations of hospital stay (13.15±2.77 vs. 27.92±3.18 days), vasopressor use (1.76±0.24 vs. 3.43 ± 1.01 days), mechanical ventilation (3.02±1.63 vs. 5.94 ± 2.11 days) and oliguria (6.57±2.45 vs. 15.29 ± 3.51 days) were reduced, and renal function more often recovered (85.1% vs. 53.1%), in the HVHF group compared with the IHD group (P < 0.05). These results raise the possibility that HVHF plus IHD may be superior to IHD alone for the treatment of acute wasp stings complicated by MODS; additional prospective studies are merited to explore this further. PMID:26207371

  9. [Role of genetic polymorphisms of the hemostatic system in the development of multiple organ dysfunctions in acute disseminated intravascular coagulation].

    PubMed

    Vorob'eva, N A; Kapustin, S I

    2007-01-01

    The paper deals with the hereditary predisposition of the hemostatic system to the severe course of acute disseminated intravascular coagulation (DIC). The results of evaluation of some types of genetic polymorphisms of the factors of coagulation and of the fibrinolytic system are recent and important for clinical application. Analysis of mortality in the fulminant course of acute DIC showed significant differences in the detection rates of the variants of genetic polymorphism in the type I plasminogen activator inhibitor gene, which is indicative of the possible genetic determination of acute DIC.

  10. Organ dysfunction during continuous veno-venous high cut-off hemodialysis in patients with septic acute kidney injury: A prospective observational study

    PubMed Central

    Chelazzi, Cosimo; Morettini, Elena; Zamidei, Lucia; Valente, Serafina; Caldini, A. Lucia; Zagli, Giovanni; De Gaudio, A. Raffaele; Romagnoli, Stefano

    2017-01-01

    Background Continuous veno-venous hemodialysis with high cut-off membranes (HCO-CVVHD) removes inflammatory mediators involved in organ dysfunction during sepsis. The aim of the present study was to assess the variations in SOFA score and identify early predictors of short-term mortality in a cohort of patients with septic shock, treated with HCO-CVVHD for acute kidney injury (AKI). Methods An observational prospective multicenter cohort study was conducted in four mixed medical-surgical ICUs. Thirty-eight patients with septic shock and AKI (KDIGO stage≥1) treated with HCO-CVVHD have been included in this study. Patients were divided into Survivors and non-Survivors according to mortality observed at 72nd hr of treatment. The variation of SOFA scores and clinical/biochemical parameters were described over time for the entire population and specifically for Survivors and non-Survivors. Similarly, circulating inflammatory mediators (as IL-6, TNF-a and IL-10) were described over time. A logistic regression analysis was used to identify the baseline clinical and biochemical parameters associated with 72 hrs-ICU mortality. Results Overall, the mean SOFA score was 12±3 at baseline, 10.9±3 at 6hrs, 9.8±3 at 12hrs, 8.9±3.3 at 24 hrs, and 8±3.5 at 48 hrs after HCO-CVVHD initiation; and 6.5±2.7 at 24 hrs and 6.6±3 at 48 hrs after HCO-CVVHD discontinuation. In the multivariate regression analysis, baseline serum lactate levels and AKI stage independently correlated with short-term mortality during HCO-CVVHD. A significant reduction was observed in circulating levels of TNFα and IL-6 among Survivors. Conclusions SOFA score significantly decreased early after initiation of HCO-CVVHD in patients with septic AKI. Baseline lactate levels and the AKI stage resulted to be associated to 72 hrs-ICU-mortality. PMID:28207795

  11. Hashimoto's Encephalopathy Presenting with Acute Cognitive Dysfunction and Convulsion.

    PubMed

    Kang, Woo-Hyuk; Na, Ju-Young; Kim, Meyung-Kug; Yoo, Bong-Goo

    2013-12-01

    Hashimoto's encephalopathy is an immune-mediated disorder characterized by acute or subacute encephalopathy related to increased anti-thyroid antibodies. Clinical manifestations of Hashimoto's encephalopathy may include stroke-like episodes, altered consciousness, psychosis, myoclonus, abnormal movements, seizures, and cognitive dysfunction. Acute cognitive dysfunction with convulsion as initial clinical manifestations of Hashimoto's encephalopathy is very rare. We report a 65-year-old man who developed acute onset of cognitive decline and convulsion due to Hashimoto's encephalopathy.

  12. The PIRO (predisposition, insult, response, organ dysfunction) model

    PubMed Central

    Marshall, John C

    2014-01-01

    Multimodal therapy for diseases like cancer has only become practicable following the development of staging systems like the TNM (tumor, nodes, metastases) system. Staging enables the identification of subgroups of patients with a disease who not only have a differing prognosis, but who are also more likely to benefit from a specific therapeutic modality. Critically ill patients represent a highly heterogeneous population for whom multiple therapeutic options are potentially available, each carrying not only the potential for differential benefit, but also the potential for differential harm. The PIRO system (predisposition, insult, response, organ dysfunction) is a template proposal for a staging system for acute illness that incorporates assessment of pre-morbid baseline susceptibility (predisposition), the specific disorder responsible for acute illness (insult), the response of the host to that insult, and the resulting degree of organ dysfunction. However the creation of a valid, robust, and clinically useful system presents significant challenges arising from the complexity of the disease state, the lack of a clear phenotype, the confounding influence of the effects of therapy and of cultural and socio-economic factors, and the relatively low profile of acute illness with clinicians and the general public. This review summarizes the rationale for such a model of illness stratification and the results of preliminary cohort studies testing the concept. It further proposes two strategies for building a staging system, recognizing that this will be a demanding undertaking that will require decades of work. PMID:24184604

  13. Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction.

    PubMed

    Elsheshtawy, Moustafa; Sriganesh, Priatharsini; Virparia, Vasudev; Patel, Falgun; Khanna, Ashok

    2016-01-01

    Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools.

  14. Antibiotic dosing in multiple organ dysfunction syndrome.

    PubMed

    Ulldemolins, Marta; Roberts, Jason A; Lipman, Jeffrey; Rello, Jordi

    2011-05-01

    Although early and appropriate antibiotic therapy remains the cornerstone of success for the treatment of septic shock, few data exist to guide antibiotic dose optimization in critically ill patients, particularly those with multiple organ dysfunction syndrome (MODS). It is well known that MODS significantly alters the patient's physiology, but the effects of these variations on pharmacokinetics have not been reviewed concisely. Therefore, the aims of this article are to summarize the disease-driven variations in pharmacokinetics and pharmacodynamics and to provide antibiotic dosing recommendations for critically ill patients with MODS. The main findings of this review are that the two parameters that vary with greatest significance in critically ill patients with MODS are drug volume of distribution and clearance. Disease- and clinician-driven changes lead to an increased volume of distribution and lower-than-expected plasma drug concentrations during the first day of therapy at least. Decreased antibiotic clearance is common and can lead to drug toxicity. In summary, "front-loaded" doses of antibiotic during the first 24 h of therapy should account for the likely increases in the antibiotic volume of distribution. Thereafter, maintenance dosing must be guided by drug clearance and adjusted to the degree of organ dysfunction.

  15. Acute massive mitral regurgitation from prosthetic valve dysfunction.

    PubMed Central

    Cooper, D K; Sturridge, M F

    1976-01-01

    Two cases of prosthetic valve dysfunction resulting in acute massive mitral regurgitation are reported; emergency operation was successful in both cases. Survival following complete dislodgement of the occluder of a disc valve, as occurred in one case, does not appear to have been reported before. The diffculty in diagnosis of sudden cardiac decompensation in patients with prosthetic valves is stressed, as is the need for urgent operation. Images PMID:973894

  16. Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction

    PubMed Central

    Sriganesh, Priatharsini; Virparia, Vasudev; Patel, Falgun; Khanna, Ashok

    2016-01-01

    Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools. PMID:27119030

  17. [Organ damage and cardiorenal syndrome in acute heart failure].

    PubMed

    Casado Cerrada, Jesús; Pérez Calvo, Juan Ignacio

    2014-03-01

    Heart failure is a complex syndrome that affects almost all organs and systems of the body. Signs and symptoms of organ dysfunction, in particular kidney dysfunction, may be accentuated or become evident for the first time during acute decompensation of heart failure. Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney, regardless of which of the two organs may have suffered the initial damage and regardless also of their previous functional status. Research into the mechanisms regulating the complex relationship between the two organs is prompting the search for new biomarkers to help physicians detect renal damage in subclinical stages. Hence, a preventive approach to renal dysfunction may be adopted in the clinical setting in the near future. This article provides a general overview of cardiorenal syndrome and an update of the physiopathological mechanisms involved. Special emphasis is placed on the role of visceral congestion as an emergent mechanism in this syndrome.

  18. Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction.

    PubMed

    Sun, Fang; Xiong, Shiqiang; Zhu, Zhiming

    2016-04-25

    Chili peppers have a long history of use for flavoring, coloring, and preserving food, as well as for medical purposes. The increased use of chili peppers in food is very popular worldwide. Capsaicin is the major pungent bioactivator in chili peppers. The beneficial effects of capsaicin on cardiovascular function and metabolic regulation have been validated in experimental and population studies. The receptor for capsaicin is called the transient receptor potential vanilloid subtype 1 (TRPV1). TRPV1 is ubiquitously distributed in the brain, sensory nerves, dorsal root ganglia, bladder, gut, and blood vessels. Activation of TRPV1 leads to increased intracellular calcium signaling and, subsequently, various physiological effects. TRPV1 is well known for its prominent roles in inflammation, oxidation stress, and pain sensation. Recently, TRPV1 was found to play critical roles in cardiovascular function and metabolic homeostasis. Experimental studies demonstrated that activation of TRPV1 by capsaicin could ameliorate obesity, diabetes, and hypertension. Additionally, TRPV1 activation preserved the function of cardiometabolic organs. Furthermore, population studies also confirmed the beneficial effects of capsaicin on human health. The habitual consumption of spicy foods was inversely associated with both total and certain causes of specific mortality after adjustment for other known or potential risk factors. The enjoyment of spicy flavors in food was associated with a lower prevalence of obesity, type 2 diabetes, and cardiovascular diseases. These results suggest that capsaicin and TRPV1 may be potential targets for the management of cardiometabolic vascular diseases and their related target organs dysfunction.

  19. Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction

    PubMed Central

    Sun, Fang; Xiong, Shiqiang; Zhu, Zhiming

    2016-01-01

    Chili peppers have a long history of use for flavoring, coloring, and preserving food, as well as for medical purposes. The increased use of chili peppers in food is very popular worldwide. Capsaicin is the major pungent bioactivator in chili peppers. The beneficial effects of capsaicin on cardiovascular function and metabolic regulation have been validated in experimental and population studies. The receptor for capsaicin is called the transient receptor potential vanilloid subtype 1 (TRPV1). TRPV1 is ubiquitously distributed in the brain, sensory nerves, dorsal root ganglia, bladder, gut, and blood vessels. Activation of TRPV1 leads to increased intracellular calcium signaling and, subsequently, various physiological effects. TRPV1 is well known for its prominent roles in inflammation, oxidation stress, and pain sensation. Recently, TRPV1 was found to play critical roles in cardiovascular function and metabolic homeostasis. Experimental studies demonstrated that activation of TRPV1 by capsaicin could ameliorate obesity, diabetes, and hypertension. Additionally, TRPV1 activation preserved the function of cardiometabolic organs. Furthermore, population studies also confirmed the beneficial effects of capsaicin on human health. The habitual consumption of spicy foods was inversely associated with both total and certain causes of specific mortality after adjustment for other known or potential risk factors. The enjoyment of spicy flavors in food was associated with a lower prevalence of obesity, type 2 diabetes, and cardiovascular diseases. These results suggest that capsaicin and TRPV1 may be potential targets for the management of cardiometabolic vascular diseases and their related target organs dysfunction. PMID:27120617

  20. Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction

    PubMed Central

    de Matos, Ana Cristina Carvalho; Requião-Moura, Lúcio Roberto; Clarizia, Gabriela; Durão, Marcelino de Souza; Tonato, Eduardo José; Chinen, Rogério; de Arruda, Érika Ferraz; Filiponi, Thiago Corsi; Pires, Luciana Mello de Mello Barros; Bertocchi, Ana Paula Fernandes; Pacheco-Silva, Alvaro

    2015-01-01

    ABSTRACT Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction. PMID:26154553

  1. Reversible anuric acute kidney injury secondary to acute renal autoregulatory dysfunction.

    PubMed

    Imbriano, Louis J; Maesaka, John K; Drakakis, James; Mattana, Joseph

    2014-02-01

    Autoregulation of glomerular capillary pressure via regulation of the resistances at the afferent and efferent arterioles plays a critical role in maintaining the glomerular filtration rate over a wide range of mean arterial pressure. Angiotensin II and prostaglandins are among the agents which contribute to autoregulation and drugs which interfere with these agents may have a substantial impact on afferent and efferent arteriolar resistance. We describe a patient who suffered an episode of anuric acute kidney injury following exposure to a nonsteroidal anti-inflammatory agent while on two diuretics, an angiotensin-converting enzyme inhibitor, and an angiotensin receptor blocker. The episode completely resolved and we review some of the mechanisms by which these events may have taken place and suggest the term "acute renal autoregulatory dysfunction" to describe this syndrome.

  2. Comparison between primary angioplasty and thrombolytic therapy on erectile dysfunction after acute ST elevation myocardial infarction

    PubMed Central

    Akdemir, Ramazan; Karakurt, Özlem; Orcan, Salih; Karakoyunlu, Nihat; Mucahit Balci, Mustafa; Sağnak, Levent; Ersoy, Hamit; Bulent Vatan, Mehmet; Kilic, Harun; Yeter, Ekrem

    2012-01-01

    Acute ST elevation myocardial infarction has high mortality and morbidity rates. The majority of patients with this condition face erectile dysfunction in addition to other health problems. In this study, we aimed to investigate the effects of two different reperfusion strategies, primary angioplasty and thrombolytic therapy, on the prevalence of erectile dysfunction after acute myocardial infarction. Of the 71 patients matching the selection criteria, 45 were treated with primary coronary angioplasty with stenting, and 26 were treated with thrombolytic agents. Erectile function was evaluated using the International Index of Erectile Function in the hospital to characterize each patient's sexual function before the acute myocardial infarction and 6 months after the event. The time required to restore blood flow to the artery affected by the infarct was found to be associated with the occurrence of erectile dysfunction after acute myocardial infarction. The increase in the prevalence of erectile dysfunction after acute myocardial infarction was 44.4% in the angioplasty group and 76.9% in the thrombolytic therapy group (P=0.008). In conclusion, this study has shown that reducing the time of reperfusion decreases the erectile dysfunction prevalence, and primary angioplasty is superior to thrombolytic therapy for decreasing the prevalence of erectile dysfunction after acute myocardial infarction. PMID:22796737

  3. Organic nitrates: update on mechanisms underlying vasodilation, tolerance and endothelial dysfunction.

    PubMed

    Münzel, Thomas; Steven, Sebastian; Daiber, Andreas

    2014-12-01

    Given acutely, organic nitrates, such as nitroglycerin (GTN), isosorbide mono- and dinitrates (ISMN, ISDN), and pentaerythrityl tetranitrate (PETN), have potent vasodilator and anti-ischemic effects in patients with acute coronary syndromes, acute and chronic congestive heart failure and arterial hypertension. During long-term treatment, however, side effects such as nitrate tolerance and endothelial dysfunction occur, and therapeutic efficacy of these drugs rapidly vanishes. Recent experimental and clinical studies have revealed that organic nitrates per se are not just nitric oxide (NO) donors, but rather a quite heterogeneous group of drugs considerably differing for mechanisms underlying vasodilation and the development of endothelial dysfunction and tolerance. Based on this, we propose that the term nitrate tolerance should be avoided and more specifically the terms of GTN, ISMN and ISDN tolerance should be used. The present review summarizes preclinical and clinical data concerning organic nitrates. Here we also emphasize the consequences of chronic nitrate therapy on the supersensitivity of the vasculature to vasoconstriction and on the increased autocrine expression of endothelin. We believe that these so far rather neglected and underestimated side effects of chronic therapy with at least GTN and ISMN are clinically important.

  4. Renal Dysfunction and Thrombolytic Therapy in Patients With Acute Ischemic Stroke

    PubMed Central

    Hao, Zilong; Yang, Chunsong; Liu, Ming; Wu, Bo

    2014-01-01

    Abstract Renal dysfunction is a prevalent comorbidity in acute ischemic stroke patients requiring thrombolytic therapy. However, the effect of renal dysfunction on the clinical outcome of this population remains controversial. This study aimed to evaluate the safety and effectiveness of thrombolytic therapy in acute stroke patients with renal dysfunction using a meta-analysis. We systematically searched PubMed and EMBASE for studies that evaluated the relationship between renal dysfunction and intravenous tissue plasminogen activator (tPA) in patients with acute ischemic stroke. Poor outcome (modified Rankin Scale ≥2), mortality, and symptomatic intracranial hemorrhage (ICH) and any ICH were analyzed. Fourteen studies were included (N = 53,553 patients). The mean age ranged from 66 to 75 years. The proportion of male participants was 49% to 74%. The proportion of renal dysfunction varied from 21.9% to 83% according to different definitions. Based on 9 studies with a total of 7796 patients, the meta-analysis did not identify a significant difference in the odds of poor outcome (odds ratio [OR] = 1.06; 95% confidence interval [CI]: 0.96–1.16; I2 = 44.5) between patients with renal dysfunction and those without renal dysfunction. Patients with renal dysfunction were more likely to die after intravenous thrombolysis (OR = 1.13; 95% CI: 1.05–1.21; I2 = 70.3). No association was observed between symptomatic ICH (OR = 1.02; 95% CI: 0.94–1.10; I2 = 0) and any ICH (OR = 1.07; 95% CI: 0.96–1.18; I2 = 25.8). Renal dysfunction does not increase the risk of poor outcome and ICH after stroke thrombolysis. Renal dysfunction should not be a contraindication for administration of intravenous thrombolysis to eligible patients. PMID:25526464

  5. Postpartum Acute Liver Dysfunction: A Case of Acute Fatty Liver of Pregnancy Developing Massive Intrahepatic Calcification.

    PubMed

    Bhat, Khalid Javid; Shovkat, Rabia; Samoon, Hamad Jeelani

    2015-12-01

    The function of the liver is particularly affected by the unique physiologic milieu of the pregnancy. Pregnancy-related liver diseases encompass a spectrum of different etiologies that are related to gestation or one of its complications. Hepatic calcification, a rare entity, is usually associated with infectious, vascular, or neoplastic lesions in the liver. To the best of our knowledge, only one case of rapidly occurring pregnancy-related intrahepatic calcification has been documented in a patient with severe eclampsia or hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome. Here we present a case of immediate "postpartum" acute fatty liver of pregnancy (AFLP) in a 23-year-old hypertensive primigravida, complicated by acute renal dysfunction who developed dense intrahepatic calcification in less than a month after the initial diagnosis. A multidisciplinary approach for the management was used, to which the patient responded aptly. This case illustrates the first description of intrahepatic calcification in AFLP syndrome and highlights some of the challenges met in making the final diagnosis.

  6. Subclavian steal syndrome presenting as recurrent pulmonary oedema associated with acute left ventricular diastolic dysfunction.

    PubMed

    Mangialavori, Giuseppe; Ballo, Piercarlo; Michelagnoli, Stefano; Ercolini, Leonardo; Barbanti, Enrico; Passuello, Franco; Abbondanti, Alessandro; Consoli, Lorenzo; Chechi, Tania; Fibbi, Veronica; Nannini, Marco; Chiodi, Leandro; Zuppiroli, Alfredo

    2013-01-01

    Subclavian steal syndrome typically presents as angina in patients with internal mammary artery grafts. Atypical clinical presentations have been rarely described. We report an unusual case of subclavian steal syndrome presenting as pulmonary oedema with acute left ventricular diastolic dysfunction and preserved ejection fraction in a patient with internal mammary artery graft and severe stenosis of the proximal left subclavian artery. After successful angioplasty and stenting of subclavian artery, the patient remained asymptomatic for six months, but then experienced acute diastolic dysfunction and recurrent pulmonary oedema associated with critical subclavian in-stent restenosis with stent deformation. This report points out that, in patients with internal mammary-to-LAD grafts, subclavian steal syndrome may present as acute left ventricular diastolic dysfunction and pulmonary oedema even in the presence of normal ejection fraction.

  7. Acute right ventricular dysfunction: real-time management with echocardiography.

    PubMed

    Krishnan, Sundar; Schmidt, Gregory A

    2015-03-01

    In critically ill patients, the right ventricle is susceptible to dysfunction due to increased afterload, decreased contractility, or alterations in preload. With the increased use of point-of-care ultrasonography and a decline in the use of pulmonary artery catheters, echocardiography can be the ideal tool for evaluation and to guide hemodynamic and respiratory therapy. We review the epidemiology of right ventricular failure in critically ill patients; echocardiographic parameters for evaluating the right ventricle; and the impact of mechanical ventilation, fluid therapy, and vasoactive infusions on the right ventricle. Finally, we summarize the principles of management in the context of right ventricular dysfunction and provide recommendations for echocardiography-guided management.

  8. Sensorineural Organs Dysfunction and Cognitive Decline: A Review Article

    PubMed Central

    Wongrakpanich, Supakanya; Petchlorlian, Aisawan; Rosenzweig, Andrew

    2016-01-01

    Vision, hearing, olfaction, and cognitive function are essential components of healthy and successful aging. Multiple studies demonstrate relationship between these conditions with cognitive function. The present article focuses on hearing loss, visual impairment, olfactory loss, and dual sensory impairments in relation to cognitive declination and neurodegenerative disorders. Sensorineural organ impairment is a predictive factor for mild cognitive impairment and neurodegenerative disorders in the elderly. We recommend early detection of sensorineural dysfunction by history, physical examination, and screening tests. Assisted device and early cognitive rehabilitation may be beneficial. Future research is warranted in order to explore advanced treatment options and method to slow progression for cognitive declination and sensorineural organ impairment. PMID:28053826

  9. Case Studies in Cardiac Dysfunction After Acute Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Hamilton, Jason C.; Korn-Naveh, Lauren; Crago, Elizabeth A.

    2015-01-01

    Patients with acute aneurysmal subarachnoid hemorrhage (SAH) often present with more than just neurological compromise. A wide spectrum of complicating cardiopulmonary abnormalities have been documented in patients with acute SAH, presenting additional challenges to the healthcare providers who attempt to treat and stabilize these patients. The patients described in this article presented with both acute aneurysmal SAH and cardiopulmonary compromise. Education and further research on this connection is needed to provide optimal care and outcomes for this vulnerable population. Nurses play a key role in balancing the critical and diverse needs of patients presenting with these symptoms. PMID:18856247

  10. Downregulation of Glutathione Biosynthesis Contributes to Oxidative Stress and Liver Dysfunction in Acute Kidney Injury

    PubMed Central

    Siow, Yaw L.; Isaak, Cara K.

    2016-01-01

    Ischemia-reperfusion is a common cause for acute kidney injury and can lead to distant organ dysfunction. Glutathione is a major endogenous antioxidant and its depletion directly correlates to ischemia-reperfusion injury. The liver has high capacity for producing glutathione and is a key organ in modulating local and systemic redox balance. In the present study, we investigated the mechanism by which kidney ischemia-reperfusion led to glutathione depletion and oxidative stress. The left kidney of Sprague-Dawley rats was subjected to 45 min ischemia followed by 6 h reperfusion. Ischemia-reperfusion impaired kidney and liver function. This was accompanied by a decrease in glutathione levels in the liver and plasma and increased hepatic lipid peroxidation and plasma homocysteine levels. Ischemia-reperfusion caused a significant decrease in mRNA and protein levels of hepatic glutamate-cysteine ligase mediated through the inhibition of transcription factor Nrf2. Ischemia-reperfusion inhibited hepatic expression of cystathionine γ-lyase, an enzyme responsible for producing cysteine (an essential precursor for glutathione synthesis) through the transsulfuration pathway. These results suggest that inhibition of glutamate-cysteine ligase expression and downregulation of the transsulfuration pathway lead to reduced hepatic glutathione biosynthesis and elevation of plasma homocysteine levels, which, in turn, may contribute to oxidative stress and distant organ injury during renal ischemia-reperfusion. PMID:27872680

  11. Evaluation of young men with organic erectile dysfunction.

    PubMed

    Papagiannopoulos, Dimitri; Khare, Narenda; Nehra, Ajay

    2015-01-01

    Erectile dysfunction (ED) in men under the age of 40 was once thought to be entirely psychogenic. Over the last few decades, advances in our understanding of erectile physiology and improvements in diagnostic testing have restructured our understanding of ED and its etiologies. Although psychogenic ED is more prevalent in the younger population, at least 15%-20% of these men have an organic etiology. Organic ED has been shown to be a predictor of increased future morbidity and mortality. As such, a thorough work-up should be employed for any man with complaints of sexual dysfunction. Oftentimes a treatment plan can be formulated after a focused history, physical exam and basic lab-work are conducted. However, in certain complex cases, more testing can be employed. The major organic etiologies can be subdivided into vascular, neurologic, and endocrine. Specific testing should be directed by clinical clues noted during the preliminary evaluation. These tests vary in degree of invasiveness, precision, and at times may not affect treatment. Results should be integrated into the overall clinical picture to assist in diagnosis and help guide therapy.

  12. Anatomical features of acute mitral valve repair dysfunction: Additional value of three-dimensional echocardiography.

    PubMed

    Derkx, Salomé; Nguyen, Virginia; Cimadevilla, Claire; Verdonk, Constance; Lepage, Laurent; Raffoul, Richard; Nataf, Patrick; Vahanian, Alec; Messika-Zeitoun, David

    2017-03-01

    Recurrence of mitral regurgitation after mitral valve repair is correlated with unfavourable left ventricular remodelling and poor outcome. This pictorial review describes the echocardiographic features of three types of acute mitral valve repair dysfunction, and the additional value of three-dimensional echocardiography.

  13. Acute Chlorine Gas Exposure Produces Transient Inflammation and a Progressive Alteration in Surfactant Composition with Accompanying Mechanical Dysfunction

    PubMed Central

    Massa, Christopher B; Scott, Pamela; Abramova, Elena; Gardner, Carol; Laskin, Debra L; Gow, Andrew J

    2014-01-01

    Acute Cl2 exposure following industrial accidents or military/terrorist activity causes pulmonary injury and severe acute respiratory distress. Prior studies suggest that antioxidant depletion is important in producing dysfunction, however a pathophysiologic mechanism has not been elucidated. We propose that acute Cl2 inhalation leads to oxidative modification of lung lining fluid, producing surfactant inactivation, inflammation and mechanical respiratory dysfunction at the organ level. C57BL/6J mice underwent whole-body exposure to an effective 60 ppm-hour Cl2 dose, and were sacrificed 3, 24 and 48 hours later. Whereas pulmonary architecture and endothelial barrier function were preserved, transient neutrophilia, peaking at 24 hours, was noted. Increased expression of ARG1, CCL2, RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells with peak change in all genes at 24 hours. Cl2 exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO3− or NO2−. Expression of the alternative macrophage activation markers, Relm-α and mannose receptor was increased in alveolar macrophages and pulmonary epithelium. Capillary surfactometry demonstrated impaired surfactant function, and altered BAL phospholipid and surfactant protein content following exposure. Organ level respiratory function was assessed by forced oscillation technique at 5 end expiratory pressures. Cl2 exposure had no significant effect on either airway or tissue resistance. Pulmonary elastance was elevated with time following exposure and demonstrated PEEP refractory derecruitment at 48 hours, despite waning inflammation. These data support a role for surfactant inactivation as a physiologic mechanism underlying respiratory dysfunction following Cl2 inhalation. PMID:24582687

  14. Organ protection possibilities in acute heart failure.

    PubMed

    Montero-Pérez-Barquero, M; Morales-Rull, J L

    2016-04-01

    Unlike chronic heart failure (HF), the treatment for acute HF has not changed over the last decade. The drugs employed have shown their ability to control symptoms but have not achieved organ protection or managed to reduce medium to long-term morbidity and mortality. Advances in our understanding of the pathophysiology of acute HF suggest that treatment should be directed not only towards correcting the haemodynamic disorders and achieving symptomatic relief but also towards preventing organ damage, thereby counteracting myocardial remodelling and cardiac and extracardiac disorders. Compounds that exert vasodilatory and anti-inflammatory action in the acute phase of HF and can stop cell death, thereby boosting repair mechanisms, could have an essential role in organ protection.

  15. Prospective investigation of pituitary functions in patients with acute infectious meningitis: is acute meningitis induced pituitary dysfunction associated with autoimmunity?

    PubMed

    Tanriverdi, F; De Bellis, A; Teksahin, H; Alp, E; Bizzarro, A; Sinisi, A A; Bellastella, G; Paglionico, V A; Bellastella, A; Unluhizarci, K; Doganay, M; Kelestimur, F

    2012-12-01

    Previous case reports and retrospective studies suggest that pituitary dysfunction may occur after acute bacterial or viral meningitis. In this prospective study we assessed the pituitary functions, lipid profile and anthropometric measures in adults with acute bacterial or viral meningitis. Moreover, in order to investigate whether autoimmune mechanisms could play a role in the pathogenesis of acute meningitis-induced hypopituitarism we also investigated the anti-pituitary antibodies (APA) and anti-hypothalamus antibodies (AHA) prospectively. Sixteen patients (10 males, 6 females; mean ± SD age 40.9 ± 15.9) with acute infectious meningitis were included and the patients were evaluated in the acute phase, and at 6 and 12 months after the acute meningitis. In the acute phase 18.7% of the patients had GH deficiency, 12.5% had ACTH and FSH/LH deficiencies. At 12 months after acute meningitis 6 of 14 patients (42.8%) had GH deficiency, 1 of 14 patients (7.1%) had ACTH and FSH/LH deficiencies. Two of 14 patients (14.3%) had combined hormone deficiencies and four patients (28.6%) had isolated hormone deficiencies at 12 months. Four of 9 (44.4%) hormone deficiencies at 6 months were recovered at 12 months, and 3 of 8 (37.5%) hormone deficiencies at 12 months were new-onset hormone deficiencies. At 12 months there were significant negative correlations between IGF-I level vs. LDL-C, and IGF-I level vs. total cholesterol. The frequency of AHA and APA positivity was substantially high, ranging from 35 to 50% of the patients throughout the 12 months period. However there were no significant correlations between AHA or APA positivity and hypopituitarism. The risk of hypopituitarism, GH deficiency in particular, is substantially high in the acute phase, after 6 and 12 months of the acute infectious meningitis. Moreover we found that 6th month after meningitis is too early to make a decision for pituitary dysfunction and these patients should be screened for at least 12 months

  16. Elevation of CXCR3-binding chemokines in urine indicates acute renal-allograft dysfunction.

    PubMed

    Hu, Huaizhong; Aizenstein, Brian D; Puchalski, Alice; Burmania, Jeanine A; Hamawy, Majed M; Knechtle, Stuart J

    2004-03-01

    A noninvasive urinary test that diagnoses acute renal allograft dysfunction would benefit renal transplant patients. We aimed to develop a rapid urinary diagnostic test by detecting chemokines. Seventy-three patients with renal allograft dysfunction prompting biopsy and 26 patients with stable graft function were recruited. Urinary levels of CXCR3-binding chemokines, monokine induced by IFN-gamma (Mig/CXCL9), IFN-gamma-induced protein of 10 kDa (IP-10/CXCL10), and IFN-inducible T-cell chemoattractant (I-TAC/CXCL11), were determined by a particle-based triplex assay. IP-10, Mig and I-TAC were significantly elevated in renal graft recipients with acute rejection, acute tubular injury and BK virus nephritis. Using 100 pg/mL as the threshold level, both IP-10 and Mig had diagnostic value (sensitivity 86.4%; specificity 91.3%) in differentiating acute graft dysfunction from other clinical conditions. In terms of monitoring the response to antirejection therapy, this urinary test is more sensitive and predictive than serum creatinine. These results indicate that this rapid test is clinically useful.

  17. Target organ damage in acute heart failure.

    PubMed

    Casado Cerrada, J; Zabaleta Camino, J P; Fontecha Ortega, M

    2016-03-01

    Acute heart failure is a prognostic factor due to its high mortality during the acute phase and the increased frequency of medium to long-term adverse events. The pathophysiological mechanisms triggered during these exacerbations can persist after reaching clinical stability, remaining even after the acute episode has ended. A certain degree of neurohormonal activation, oxidative stress, apoptosis and inflammation (among other conditions) can therefore persist, resulting in organ damage, not just of the myocardium but likely the entire cardiovascular apparatus. This new insight into the persistence of harmful mechanisms that last beyond the exacerbations could be the start of a change in perspective for developing new therapeutic strategies that seek an overall control of hemodynamic and congestive changes that occur during acute decompensated heart failure and changes that remain after achieving clinical stability.

  18. Peritoneal dialysis treatment for severe lupus nephritis patients complicated with essential organ dysfunction.

    PubMed

    Zhou, Yan; Yu, Yusheng; Tang, Zheng; Li, Shijun; Hu, Weixin; Luo, Chunlei; Liu, Zhihong

    2015-12-01

    The aim of the present study was to evaluate the clinical efficacy of peritoneal dialysis (PD) in patients with severe lupus nephritis (LN) complicated with organ dysfunction. In total, 13 severe LN patients complicated with multiple-organ dysfunction, who underwent PD treatment between November 2003 and September 2010, were enrolled in the study. Six patients received methylprednisolone pulse therapy due to lupus activity and progressive renal failure. These patients were complicated with severe edema, cardiac insufficiency and severe hypoalbuminemia. PD was applied to the patients, followed by the administration of immunosuppressants. Patients were followed-up to review the parameters of renal function, the immunological indexes and the systemic lupus erythematosus disease activity index. The results indicated that the general state of health was markedly improved following PD treatment, with edema abatement and improvement of heart function and physical strength. Serum creatinine levels significantly decreased from 6.3±1.6 to 2.6±1.0 mg/dl. A total of 10 cases ceased PD treatment during the follow-up, while three cases continued PD to the end of the follow-up period. The levels of albumin and hemoglobin exhibited a marked increase from 29.7±5.7 to 35.2±5.5 g/l and 8.7±1.8 to 9.8±1.8 g/l, respectively. There was one case of peritonitis, one case of peritoneal leakage and two cases of pneumonia. Therefore, PD may be a successful treatment method for severe LN patients complicated with essential organ dysfunction. PD not only improved the symptoms of edema and heart failure, but also played an important role in preserving residual renal function and improving the nutritional state of the patients. Thus, PD can be considered as a treatment option for patients with severe LN associated with acute kidney injury, however, selecting a suitable immunosuppressant during PD treatment is essential.

  19. Multiple organ dysfunction syndrome, an unusual complication of heroin intoxication: a case report and review of literature.

    PubMed

    Feng, Gang; Luo, Qiancheng; Guo, Enwei; Yao, Yulan; Yang, Feng; Zhang, Bingyu; Li, Longxuan

    2015-01-01

    Multiple organ dysfunction syndrome (MODS) has rarely been described in patients with heroin intoxication. Here, we report a rare case of MODS involving six organs, due to heroin intoxication. The patient was a 32-year-old Chinese man with severe heroin intoxication complicated by acute pulmonary edema and respiratory insufficiency, shock, myocardial damage and cardiac insufficiency, rhabdomyolysis and acute renal insufficiency, acute liver injury and hepatic insufficiency, toxic leukoencephalopathy, and hypoglycemia. He managed to survive and was discharged after 10 weeks of intensive care. The possible pathogenesis and therapeutic measures of MODS induced by heroin intoxication and some suggestions for preventing and treating severe complications of heroin intoxication, based on clinical evidence and the pertinent literature, are discussed in this report.

  20. Involvement of AMPK in Alcohol Dehydrogenase Accentuated Myocardial Dysfunction Following Acute Ethanol Challenge in Mice

    PubMed Central

    Guo, Rui; Scott, Glenda I.; Ren, Jun

    2010-01-01

    Objectives Binge alcohol drinking often triggers myocardial contractile dysfunction although the underlying mechanism is not fully clear. This study was designed to examine the impact of cardiac-specific overexpression of alcohol dehydrogenase (ADH) on ethanol-induced change in cardiac contractile function, intracellular Ca2+ homeostasis, insulin and AMP-dependent kinase (AMPK) signaling. Methods ADH transgenic and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Oral glucose tolerance test, cardiac AMP/ATP levels, cardiac contractile function, intracellular Ca2+ handling and AMPK signaling (including ACC and LKB1) were examined. Results Ethanol exposure led to glucose intolerance, elevated plasma insulin, compromised cardiac contractile and intracellular Ca2+ properties, downregulated protein phosphatase PP2A subunit and PPAR-γ, as well as phosphorylation of AMPK, ACC and LKB1, all of which except plasma insulin were overtly accentuated by ADH transgene. Interestingly, myocardium from ethanol-treated FVB mice displayed enhanced expression of PP2Cα and PGC-1α, decreased insulin receptor expression as well as unchanged expression of Glut4, the response of which was unaffected by ADH. Cardiac AMP-to-ATP ratio was significantly enhanced by ethanol exposure with a more pronounced increase in ADH mice. In addition, the AMPK inhibitor compound C (10 µM) abrogated acute ethanol exposure-elicited cardiomyocyte mechanical dysfunction. Conclusions In summary, these data suggest that the ADH transgene exacerbated acute ethanol toxicity-induced myocardial contractile dysfunction, intracellular Ca2+ mishandling and glucose intolerance, indicating a role of ADH in acute ethanol toxicity-induced cardiac dysfunction possibly related to altered cellular fuel AMPK signaling cascade. PMID:20585647

  1. Regional right ventricular dysfunction in acute pulmonary embolism: relationship with clot burden and biomarker profile.

    PubMed

    Tuzovic, Mirela; Adigopula, Sasikanth; Amsallem, Myriam; Kobayashi, Yukari; Kadoch, Michael; Boulate, David; Krishnan, Gomathi; Liang, David; Schnittger, Ingela; Fleischmann, Dominik; McConnell, Michael V; Haddad, François

    2016-03-01

    Regional right ventricular (RV) dysfunction (RRVD) is an echocardiographic feature in acute pulmonary embolism (PE), primarily reported in patients with moderate-to-severe RV dysfunction. This study investigated the clinical importance of RRVD by assessing its relationship with clot burden and biomarkers. We identified consecutive patients admitted to the emergency department between 1999 and 2014 who underwent computed tomographic angiography, echocardiography, and biomarker testing (troponin and NT-proBNP) for suspected acute PE. RRVD was defined as normal excursion of the apex contrasting with hypokinesis of the mid-free wall segment. RV assessment included measurements of ventricular dimensions, fractional area change, free-wall longitudinal strain and tricuspid annular plane systolic excursion. Clot burden was assessed using the modified Miller score. Of 82 patients identified, 51 had acute PE (mean age 66 ± 17 years, 43% male). No patient had RV myocardial infarction. RRVD was present in 41% of PEs and absent in all patients without PE. Among patients with PE, 86% of patients with RRVD had central or multi-lobar PE. Patients with RRVD had higher prevalence of moderate-to-severe RV dilation (81 vs. 30%, p < 0.01) and dysfunction (86 vs. 23%, p < 0.01). There was a strong trend for higher troponin level in PE patients with RRVD (38 vs. 13% in PE patients without RRVD, p = 0.08), while there was no significant difference for NT-proBNP (67 vs. 73%, p = 0.88). RRVD showed good concordance between readers (87%). RRVD is associated with an increased clot burden in acute PE and is more prevalent among patients with moderate-to-severe RV enlargement and dysfunction.

  2. Measuring executive dysfunction in an acute rehabilitation setting: using the dysexecutive questionnaire (DEX).

    PubMed

    Bennett, Pauleen C; Ong, Ben; Ponsford, Jennie

    2005-07-01

    It is recognized that existing neuropsychological measures of executive dysfunction lack adequate sensitivity and selectivity. While attempts have been made to develop improved measures, these have not yet been of great value to those who need to accurately identify executive deficits in a clinical setting. Several behavioral rating scales have been developed for this reason, including the 20-item Dysexecutive Questionnaire (DEX), which forms part of the Behavioral Assessment of the Dysexecutive Syndrome (BADS) test battery. To investigate the ability of the DEX to identify executive dysfunction in an acute rehabilitation setting, the BADS was administered to 64 persons who had sustained traumatic brain injury. It was found to be almost as sensitive to executive dysfunction, as measured by the total score obtained on the BADS battery, as an extended 65-item version of the scale, when completed by either the occupational therapist or clinical neuropsychologist working with each patient. Family members and the patient themselves provided, as expected, less accurate information. Our results indicate that the DEX can be used with some confidence as a screening instrument to identify executive dysfunction in an acute rehabilitation setting, provided it is completed by professional personnel, trained to be sensitive to the cognitive and behavioral concomitants of this disorder.

  3. Obesity-induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.

    PubMed

    Shah, Dilip; Romero, Freddy; Guo, Zhi; Sun, Jianxin; Li, Jonathan; Kallen, Caleb B; Naik, Ulhas P; Summer, Ross

    2017-03-09

    Obesity is a significant risk factor for the acute respiratory distress syndrome (ARDS). The mechanisms underlying this association are unknown. We recently showed that diet-induced obese (DIO) mice exhibit pulmonary vascular endothelial dysfunction which is associated with enhanced susceptibility to lipopolysaccharide (LPS)-induced lung injury. Here, we demonstrate that lung endothelial dysfunction in DIO mice coincides with increased endoplasmic reticulum (ER) stress. Specifically, we observed enhanced expression of the major sensors of misfolded proteins including PERK, IREα and ATF6, in whole lung and in lung endothelial cells isolated from DIO mice. Further, we found that lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of DIO mice. Similar changes were observed in lung endothelial cells and in whole lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation; indicating that ER stress causes endothelial dysfunction in the lung. Treatment with 4-PBA, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in DIO mice. Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium leading to pulmonary endothelial cell dysfunction. Our work suggests that reducing protein load in the endoplasmic reticulum of pulmonary endothelial cells might protect against ARDS in obese individuals.

  4. Arginine methylation dysfunction increased risk of acute coronary syndrome in coronary artery disease population

    PubMed Central

    Zhang, Shengyu; Zhang, Shuyang; Wang, Hongyun; Wu, Wei; Ye, Yicong

    2017-01-01

    Abstract The plasma levels of asymmetric dimethylarginine (ADMA) had been proved to be an independent cardiovascular risk factor. Few studies involved the entire arginine methylation dysfunction. This study was designed to investigate whether arginine methylation dysfunction is associated with acute coronary syndrome risk in coronary artery disease population. In total 298 patients undergoing coronary angiography because of chest pain with the diagnosis of stable angina pectoris or acute coronary syndrome from February 2013 to June 2014 were included. Plasma levels of free arginine, citrulline, ornithine, and the methylated form of arginine, ADMA, and symmetric dimethylarginine (SDMA) were measured with high-performance liquid chromatography coupled with tandem mass spectrometry. We examined the relationship between arginine metabolism-related amino acids or arginine methylation index (AMI, defined as ratio of [arginine + citrulline + ornithine]/[ADMA + SDMA]) and acute coronary events. We found that plasma ADMA levels were similar in the stable angina pectoris group and the acute coronary syndrome group (P = 0.88); the AMI differed significantly between 2 groups (P < 0.001). Multivariate logistic regression demonstrated that AMI was an independent risk factor of acute coronary events in patients with coronary artery disease (OR = 0.975, 95% confidence interval 0.956–0.993; P = 0.008). Our study suggested that ADMA levels were very similar in the stable angina and acute coronary syndrome patients; AMI might be an independent risk factor of acute coronary events in coronary artery disease population. PMID:28207514

  5. Assessment of Autonomic Dysfunction in Acute Stroke Patients at a Tertiary Care Hospital

    PubMed Central

    Chidambaram, Hemachandrika; Gnanamoorthy, Kothai; Rajendran, Kannan; Pavadai, Chitrambalam

    2017-01-01

    Introduction In patients who present with acute cerebro-vascular disease, autonomic function testing is usually not given its due importance. This is because of the complex nature of the autonomic function tests and the relative technical difficulty faced in administering the tests to the patients. A simple and non-invasive method to assess the autonomic dysfunction is measurement of resting Heart Rate Variability (HRV). Aim To study the pattern of autonomic dysfunction among patients admitted with acute stroke and to study the relationship between autonomic dysfunction and the morbidity and mortality associated with acute stroke. Materials and Methods The study was carried out on 97 patients who were admitted with diagnosis of acute stroke. Patients with conduction abnormalities on ECG were excluded from the study. Resting ECG tracings were obtained for a period of 5 minutes. The frequency domain analysis of HRV was performed by a Fast Fourier transform of the RR intervals. The High Frequency (HF) was representative of the parasympathetic activity while low frequency is representative of baroreceptor mediated parasympathetic and sympathetic activity and Low Frequency (LF)/HF ratio was a measure of the sympathovagal balance. Statistical analysis was carried out with student’s t-test and chi-square test and p-value ≥ 0.05 was taken to be statistically significant. Results The mean age of the patients was 60.84±14.12 years. A total of 41 patients were females and 77 patients had ischemic stroke. Out of the total 97, 60 patients had evidence suggestive of increased sympathetic activity with a mean LF/HF ratio of 2.03±0.88. These patients had significantly higher mean systolic BP, diastolic BP and National Institute of Health Stroke Scale (NIHSS) values when compared to patients with reduced LF/HF ratio (166.33±24.81 vs 148.54±19.42, p=0.0003, 100.33±18.73 vs 88.76±12.66, p=0.0013, 15.77±8.22 vs 11.49±6.63, p=0.0088 respectively). These patients also had a

  6. Pneumonia presenting with organ dysfunctions: Causative microorganisms, host factors and outcome.

    PubMed

    Menéndez, Rosario; Montull, Beatriz; Reyes, Soledad; Amara-Elori, Isabel; Zalacain, Rafael; Capelastegui, Alberto; Aspa, Javier; Borderías, Luis; Martín-Villasclaras, Juan J; Bello, Salvador; Alfageme, Inmaculada; Rodríguez de Castro, Felipe; Rello, Jordi; Molinos, Luis; Ruiz-Manzano, Juan; Torres, Antoni

    2016-11-01

    Community-acquired pneumonia (CAP) is a serious infection that may occasionally rapidly evolve provoking organ dysfunctions. We aimed to characterize CAP presenting with organ dysfunctions at the emergency room, with regard to host factors and causative microorganisms, and its impact on 30-day mortality. 460 of 4070 (11.3%) CAP patients had ≥2 dysfunctions at diagnosis, with a 30-day mortality of 12.4% vs. 3.4% in those with one or no dysfunctions. Among them, the most frequent causative microorganisms were Streptococcus pneumoniae, gram-negatives and polymicrobial etiology. Independent host risk factors for presenting with ≥2 dysfunctions were: liver (OR 2.97) and renal diseases (OR 3.91), neurological disorders (OR 1.86), and COPD (OR 1.30). Methicillin-resistant Staphylococcus aureus (OR 6.41) and bacteraemic episodes (OR 1.68) had the higher independent risk among microorganisms. The number of organ dysfunctions vs. none increased at 30-day mortality: three organs (OR 11.73), two organs (OR 4.29), and one organ (OR 2.42) whereas Enterobacteria (OR 3.73) were also independently related to mortality. The number of organ dysfunctions was the strongest 30-day mortality risk factor while Enterobacteriaceae was also associated with poorer outcome. The assessment of organ dysfunctions in CAP should be implemented for management, allocation and treatment decisions on initial evaluation.

  7. Quantitative Evaluation of Acute Renal Transplant Dysfunction with Low-Dose Three-dimensional MR Renography

    PubMed Central

    Zhang, Jeff L.; Rusinek, Henry; Chandarana, Hersh; Vivier, Pierre-Hugues; Babb, James S.; Diflo, Thomas; John, Devon G.; Benstein, Judith A.; Barisoni, Laura; Stoffel, David R.; Lee, Vivian S.

    2011-01-01

    Purpose: To assess prospectively the ability of quantitative low-dose three-dimensional magnetic resonance (MR) renography to help identify the cause of acute graft dysfunction. Materials and Methods: This HIPAA-compliant study was approved by the institutional review board, and written informed consent was obtained. Between December 2001 and May 2009, sixty patients with transplanted kidneys (41 men and 19 women; mean age, 49 years; age range, 22–71 years) were included. Thirty-one patients had normal function and 29 had acute dysfunction due to acute rejection (n = 12), acute tubular necrosis (ATN) (n = 8), chronic rejection (n = 6), or drug toxicity (n = 3). MR renography was performed at 1.5 T with three-dimensional gradient-echo imaging. With use of a multicompartment renal model, the glomerular filtration rate (GFR) and the mean transit time (MTT) of the tracer for the vascular compartment (MTTA), the tubular compartment (MTTT), and the collecting system compartment (MTTC) were calculated. Also derived was MTT for the whole kidney (MTTK = MTTA + MTTT + MTTC) and fractional MTT of each compartment (MTTA/K = MTTA/MTTK, MTTT/K = MTTT/MTTK, MTTC/K = MTTC/MTTK). These parameters were compared in patients in the different study groups. Statistical analysis was performed by using analysis of covariance. Results: There were significant differences in GFR and MTTK between the acute dysfunction group (36.4 mL/min ± 20.8 [standard deviation] and 177.1 seconds ± 46.8, respectively) and the normal function group (65.9 mL/min ± 27.6 and 140.5 seconds ± 51.8, respectively) (P < .001 and P = .004). The MTTA/K was significantly higher in the acute rejection group (mean, 12.7% ± 2.9) than in the normal function group (mean, 8.3% ± 2.2; P < .001) or in the ATN group (mean, 7.1% ± 1.4; P < .001). The MTTT/K was significantly higher in the ATN group (mean, 83.2% ± 9.2) than in the normal function group (mean, 72.4% ± 10.2; P = .031) or in the acute rejection group

  8. MORE for multiple organ dysfunction syndrome: Multiple Organ REanimation, REgeneration, and REprogramming.

    PubMed

    Cobb, J Perren

    2010-11-01

    Those who care for the critically ill and injured rightfully celebrate the advances made by our field over its first 50 yrs. Advances in systems, tissue, and molecular engineering, together defined as "health engineering," will provide unprecedented opportunities to treat multiple organ dysfunction syndrome in the 21st century. In the future, Multiple Organ REanimation, REgeneration, and REprogramming will be responsible for new treatment approaches for those with multiple organ dysfunction syndrome; several examples are presented here. Thus, as we spent the first 50 yrs of care for the critical ill and injured learning how best to hook humans up to machines, we will spend the next 50 yrs understanding better how to liberate patients from mechanical support. It is difficult to know when these advances will be realized given that the rate of change continues to increase and the seemingly impossible goal of reprogramming fully differentiated cells was accomplished recently by manipulating a few transcription factors. It is not unrealistic to expect that in the next couple of decades that it will be possible to dedifferentiate dysfunctional somatic cells in vivo to a more robust, resistant cell phenotype. Our future should be aimed in part at refining our skill sets and refocusing (even rebranding) critical care as health engineering aimed at Multiple Organ REanimation, REgeneration, and REprogramming.

  9. Saturated hydrogen saline attenuates endotoxin-induced acute liver dysfunction in rats.

    PubMed

    Xu, X-F; Zhang, J

    2013-01-01

    To determine the effect of saturated hydrogen saline on lipopolysaccharide (LPS)-induced acute liver dysfunction, rats were divided into control, LPS, and LPS plus saturated hydrogen saline (LPS+H(2)) groups. Treatment with saturated hydrogen saline prolonged the median survival time and reduced liver dysfunction. Moreover, saturated hydrogen saline significantly reduced pathological alterations in liver tissues, the number of ballooned hepatocytes, serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels, and myeloperoxidase (MPO) and malondialdehyde (MDA) levels in liver tissues (P<0.05). Cell apoptosis was detected in liver tissues after LPS treatment, and attenuated by saturated hydrogen saline treatment. Saturated hydrogen saline also decreased phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated Jun kinase (p-JNK), nuclear factor-kappa B (NF-kappaB), and second mitochondria-derived activator of caspase (Smac) levels, and increased p38 activation (P<0.05). Thus, saturated hydrogen saline may attenuate LPS-induced acute liver dysfunction in rats, possibly by reducing inflammation and cell apoptosis. Mitogen-activated protein kinase (MAPK), NF-kappaB, and Smac may contribute to saturated hydrogen saline-mediated liver protection.

  10. After the bomb drops: A new look at radiation-induced multiple organ dysfunction syndrome (MODS)

    PubMed Central

    Williams, Jacqueline P.; McBride, William H.

    2012-01-01

    Purpose There is increasing concern that, since the Cold War era, there has been little progress regarding the availability of medical countermeasures in the event of either a radiological or nuclear incident. Fortunately, since much is known about the acute consequences that are likely to be experienced by an exposed population, the probability of survival from the immediate hematological crises after total body irradiation (TBI) has improved in recent years. Therefore focus has begun to shift towards later down-stream effects, seen in such organs as the gastrointestinal tract (GI), skin, and lung. However, the mechanisms underlying therapy-related normal tissue late effects, resulting from localised irradiation, have remained somewhat elusive and even less is known about the development of the delayed syndrome seen in the context of whole body exposures, when it is likely that systemic perturbations may alter tissue microenvironments and homeostasis. Conclusions The sequence of organ failures observed after near-lethal TBI doses are similar in many ways to that of multiple organ dysfunction syndrome (MODS), leading to multiple organ failure (MOF). In this review, we compare the mechanistic pathways that underlie both MODS and delayed normal tissue effects since these may impact on strategies to identify radiation countermeasures. PMID:21417595

  11. Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress

    PubMed Central

    2015-01-01

    Abstract Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3′,-5′-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed. Antioxid. Redox Signal. 23, 899–942. PMID:26261901

  12. Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress.

    PubMed

    Daiber, Andreas; Münzel, Thomas

    2015-10-10

    Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3',-5'-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed.

  13. Pseudo-acute myocardial infarction due to transient apical ventricular dysfunction syndrome (Takotsubo syndrome)

    PubMed Central

    Maciel, Bruno Araújo; Cidrão, Alan Alves de Lima; Sousa, Ítalo Bruno dos Santos; Ferreira, José Adailson da Silva; Messias Neto, Valdevino Pedro

    2013-01-01

    Takotsubo syndrome is characterized by predominantly medial-apical transient left ventricular dysfunction, which is typically triggered by physical or emotional stress. The present article reports the case of a 61-year-old female patient presenting with dizziness, excessive sweating, and sudden state of ill feeling following an episode involving intense emotional stress. The physical examination and electrocardiogram were normal upon admission, but the troponin I and creatine kinase-MB concentrations were increased. Acute myocardial infarction without ST segment elevation was suspected, and coronary angiography was immediately performed, which showed severe diffuse left ventricular hypokinesia, medial-apical systolic ballooning, and a lack of significant coronary injury. The patient was referred to the intensive care unit and was successfully treated with supportive therapy. As this case shows, Takotsubo syndrome might simulate the clinical manifestations of acute myocardial infarction, and coronary angiography is necessary to distinguish between both myocardial infarction and myocardial infarction in the acute stage. The present patient progressed with spontaneous resolution of the ventricular dysfunction without any sequelae. PMID:23887762

  14. Bladder dysfunction in acute transverse myelitis: magnetic resonance imaging and neurophysiological and urodynamic correlations

    PubMed Central

    Kalita, J; Shah, S; Kapoor, R; Misra, U

    2002-01-01

    Aims: To evaluate micturition abnormalities in acute transverse myelitis and correlate these with evoked potentials, magnetic resonance imaging (MRI), and urodynamic findings. Setting: Tertiary care teaching hospital. Patients: 18 patients with acute transverse myelitis, aged 4–50 years; 15 had paraparesis and three quadriparesis. Methods: Patients with acute transverse myelitis had a neurological evaluation and tibial somatosensory and motor evoked potential studies in the lower limbs. Spinal MRI was carried out using a 1.5 T scanner. Urodynamic studies were done using Dantec UD 5500 equipment. Neurological outcome was determined on the basis of Barthel index score at six months as poor, partial, or complete. In some patients, urodynamic studies were repeated at six and 12 months. Results: Spinal MRI in 14 of the 18 patients revealed T2 hyperintense signal changes extending for at least three spinal segments in 13; one patient had normal MRI. In the acute stage, 17 patients had a history of urinary retention and one had urge incontinence. On follow up at six months two patients regained normal voiding, retention persisted in six, and storage symptoms developed in 10, of whom five also had emptying difficulties. Urodynamic studies showed an areflexic or hypocontractile bladder in 10, detrusor hyperreflexia with poor compliance in two, and detrusor sphincter dyssynergia in three. Early abnormal urodynamic findings commonly persisted at the six and 12 months examinations. Persistent abnormalities included detrusor hyperreflexia, dyssynergia, and areflexic bladder. The urodynamic abnormalities correlated with muscle tone and reflex changes but not with sensory or motor evoked potentials, muscle power, MRI signal changes, sensory level, or six months outcome. Conclusions: Bladder dysfunction is common in acute transverse myelitis and may be the only sequel. Urodynamic study is helpful in evaluating the bladder dysfunction and also in its management. PMID:12122174

  15. Acute chlorine gas exposure produces transient inflammation and a progressive alteration in surfactant composition with accompanying mechanical dysfunction

    SciTech Connect

    Massa, Christopher B.; Scott, Pamela; Abramova, Elena; Gardner, Carol; Laskin, Debra L.; Gow, Andrew J.

    2014-07-01

    Acute Cl{sub 2} exposure following industrial accidents or military/terrorist activity causes pulmonary injury and severe acute respiratory distress. Prior studies suggest that antioxidant depletion is important in producing dysfunction, however a pathophysiologic mechanism has not been elucidated. We propose that acute Cl{sub 2} inhalation leads to oxidative modification of lung lining fluid, producing surfactant inactivation, inflammation and mechanical respiratory dysfunction at the organ level. C57BL/6J mice underwent whole-body exposure to an effective 60 ppm-hour Cl{sub 2} dose, and were euthanized 3, 24 and 48 h later. Whereas pulmonary architecture and endothelial barrier function were preserved, transient neutrophilia, peaking at 24 h, was noted. Increased expression of ARG1, CCL2, RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells with peak change in all genes at 24 h. Cl{sub 2} exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO{sub 3}{sup −} or NO{sub 2}{sup −}. Expression of the alternative macrophage activation markers, Relm-α and mannose receptor was increased in alveolar macrophages and pulmonary epithelium. Capillary surfactometry demonstrated impaired surfactant function, and altered BAL phospholipid and surfactant protein content following exposure. Organ level respiratory function was assessed by forced oscillation technique at 5 end expiratory pressures. Cl{sub 2} exposure had no significant effect on either airway or tissue resistance. Pulmonary elastance was elevated with time following exposure and demonstrated PEEP refractory derecruitment at 48 h, despite waning inflammation. These data support a role for surfactant inactivation as a physiologic mechanism underlying respiratory dysfunction following Cl{sub 2} inhalation. - Highlights: • Effect of 60 ppm*hr Cl{sub 2} gas on lung inflammation and mechanical function examined. • Pulmonary inflammation is transient and minor.

  16. Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage

    PubMed Central

    Song, Byoung-Joon; Moon, Kwan-Hoon; Upreti, Vijay V.; Eddington, Natalie D.; Lee, Insong J.

    2010-01-01

    Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage. PMID:20420575

  17. Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage.

    PubMed

    Song, Byoung-Joon; Moon, Kwan-Hoon; Upreti, Vijay V; Eddington, Natalie D; Lee, Insong J

    2010-08-01

    Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage.

  18. [Oliguria and acute renal dysfunction in a six-month-old infant].

    PubMed

    Cui, Ya-Jie; Song, Chun-Lan; Cheng, Yi-Bing

    2017-02-01

    The infant (a girl aged 6 months) was admitted to the hospital because of oliguria and acute renal dysfunction. The laboratory examination results showed serious metabolic acidosis and increased blood urea nitrogen and serum creatinine levels. The patient continued to be anuric after 10 days of treatment with continuous renal replacement therapy (CRRT). she died a day later. The family history showed that the patient's sister died of acute renal failure 6 months after birth. The genomic sequencing results showed AGXT mutation in the patient and confirmed the diagnosis of primary hyperoxaluria type 1 (PH1). Her parents were heterozygous carriers. PH1 should be considered when the children have abnormal renal function or recurrent renal calculi or have a family history of these symptoms. AGXT gene analysis is an important method for PH1 diagnosis.

  19. [Sacroiliac joint dysfunction presented with acute low back pain: three case reports].

    PubMed

    Hamauchi, Shuji; Morimoto, Daijiro; Isu, Toyohiko; Sugawara, Atsushi; Kim, Kyongsong; Shimoda, Yusuke; Motegi, Hiroaki; Matsumoto, Ryoji; Isobe, Masanori

    2010-07-01

    Sacroiliac joint (SIJ) can cause low back pain when its joint capsule and ligamentous tissue are damaged. We report our experience in treating three SIJ dysfunction patients presenting with acute low back pain (a 38 year-old male, a 24 year-old male, and a 32 year-old female). SIJ dysfunction was diagnosed using the one-finger test, the modified Newton test, and SIJ injection. In all three patients, lumbar MRI demonstrated slightly degenerated lumbar lesions (lumbar canal stenosis, lumbar disc hernia). Two patients had paresthesia or pain in the leg and all three patients showed iliac muscle tenderness in the groin, which was thought to be a referred symptom because of improvement after SIJ injection. The two male patients returned to work and the problems have not recurred. Although our female patient resumed daily life as a housewife, her condition recurred at intervals of 2-3 months and she required regular SIJ injections. The prevalence of SIJ dysfunction of low back pain is about 10%, so it should be considered as a differential diagnosis when treating low back pain and designing treatment for lumbar spinal disorders.

  20. Yohimbine treatment of organic erectile dysfunction in a dose-escalation trial.

    PubMed

    Guay, A T; Spark, R F; Jacobson, J; Murray, F T; Geisser, M E

    2002-02-01

    Yohimbine has had questionable effects in men with organic erectile dysfunction. We conducted this study to better define the population of men responsive to yohimbine, because tobacco was thought to affect a regimen of yohimbine more than other risk factors. We measured nocturnal penile tumescence with the RigiScan monitor, hormone profiles, answers to the Florida Sexual Health Questionnaire, and clinical responses at baseline and after two different doses of yohimbine in 18 nonsmoking men with erectile dysfunction. Of the 18 men, nine (50%) were successful in completing intercourse in more than 75% of attempts. The yohimbine responders were men with less severe erectile dysfunction as manifested by improved increased rigidity on RigiScan testing, higher Florida Sexual Health Questionnaire scores, and slightly higher levels of serum testosterone. Yohimbine is an effective therapy to treat organic erectile dysfunction in some men with erectile dysfunction.

  1. Influence of renal dysfunction on clinical outcomes in patients with congestive heart failure complicating acute myocardial infarction.

    PubMed

    Kim, Chang Seong; Kim, Min Jee; Kang, Yong Un; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon; Ahn, Young-Keun; Jeong, Myung Ho; Kim, Young Jo; Cho, Myeong Chan; Kim, Chong Jin; Kim, Soo Wan

    2013-01-01

    The clinical course and medical treatment of patients with congestive heart failure (CHF) complicating acute myocardial infarction (AMI) are not well established, especially in patients with concomitant renal dysfunction. We performed a retrospective analysis of the prospective Korean Acute Myocardial Infarction Registry to assess the medical treatments and clinical outcomes of patients with CHF (Killip classes II or III) complicated by AMI, in the presence or absence of renal dysfunction. Of 13,498 patients with AMI, 2769 (20.5%) had CHF on admission. Compared to CHF patients with preserved renal function, in-hospital mortality and major adverse cardiac events were increased both at 1 month and at 1 year after discharge in patients with renal dysfunction (1154; 41.7%). Postdischarge use of aspirin, betablockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers and statins significantly reduced the 1-year mortality rate for CHF patients with renal dysfunction; such reduction was not observed for those without renal dysfunction, except in the case of aspirin. Patients with CHF complicating AMI, which is accompanied by renal dysfunction, are at higher risk for adverse cardiovascular outcomes than patients without renal dysfunction. However, they receive fewer medications proven to reduce mortality rates.

  2. Impact of renal dysfunction and glucometabolic status on one month mortality after acute myocardial infarction.

    PubMed

    Schiele, François; Seronde, Marie France; Descotes-Genon, Vincent; Blonde, Marie-Cecile; Legalery, Pierre; Meneveau, Nicolas; Ecarnot, Fiona; Penfornis, Alfred; Ducloux, Didier; Bassand, Jean-Pierre

    2007-01-01

    Patients with impaired glucometabolic status or renal function have a higher mortality after acute myocardial infarction. It is unclear whether this higher risk is independent or related to the quality of care. In a prospective registry, stress hyperglycaemia (SH) was defined as glucose level>140 mg/dl. Renal function was assessed by the glomerular filtration rate (GFR): normal (>/=60), mild (30-60) and severe dysfunction (<30 ml/min/1.72 m(2)). The level of risk was assessed by the TIMI risk index and the quality of care by the rate of use of five guidelines-recommended treatments. Among the 1388 patients included, 23% had diabetes, 16% had SH, renal function was normal in 55%, mildly impaired in 35% and severely impaired in 9.5%. At one month, the mortality rate was higher in patients with SH (18%) as compared with diabetics (9%) or those with normal glucometabolic status (5%). Similarly, the mortality rate was higher in those with impaired renal function. Multivariable analysis identified SH, GFR group, TIMI risk index, ST segment elevation MI and quality of care as independent predictors of one-month mortality. In patients with acute MI, SH and GFR<30 ml/min/m(2) are independent predictors of mortality after adjustment for the level of risk and acute care.

  3. Usefulness of open lung biopsy in mechanically ventilated patients with undiagnosed diffuse pulmonary infiltrates: influence of comorbidities and organ dysfunction

    PubMed Central

    Lim, Seong Yong; Suh, Gee Young; Choi, Jae Chol; Koh, Won Jung; Lim, Si Young; Han, Joungho; Lee, Kyung Soo; Shim, Young Mog; Chung, Man Pyo; Kim, Hojoong; Kwon, O Jung

    2007-01-01

    Background The purpose of this study was to evaluate the clinical usefulness of open lung biopsy (OLB) in patients undergoing mechanical ventilation for diffuse pulmonary infiltrates of unknown etiology. Methods This was a 10-year retrospective study in a 10-bed medical intensive care unit. The medical records of 36 ventilator-dependent patients who underwent OLB for the diagnosis of unknown pulmonary infiltrates from 1994 to 2004 were reviewed retrospectively. Data analyzed included demographic data, Charlson age–comorbidity score, number of organ dysfunctions, Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA) score, ventilation variables, and radiological patterns. Diagnostic yield, effect on subsequent treatment changes, and complications of OLB were also assessed. Results A specific clinico-pathologic diagnosis was obtained for 31 patients (86%). The most common diagnoses were interstitial pneumonia (n = 17, including 8 acute interstitial pneumonia) and viral pneumonia (n = 4). Therapeutic modifications were made in 64% of patients. Patients who received OLB less than 1 week after initiation of mechanical ventilation were more likely to survive (63% versus 11%; P = 0.018). There were no major complications associated with the procedure. Factors independently associated with survival were the Charlson age-comorbidity score, number of organ dysfunction and the PaO2/FiO2 ratio on the day of the OLB. Conclusion OLB can provide a specific diagnosis in many ventilator-dependent patients with undiagnosed pulmonary infiltrate. Early OLB seems to be useful in critically ill patients with isolated respiratory failure. PMID:17725820

  4. Incidence and Prognostic Value of the Systemic Inflammatory Response Syndrome and Organ Dysfunctions in Ward Patients

    PubMed Central

    Zadravecz, Frank J.; Winslow, Christopher; Howell, Michael D.; Edelson, Dana P.

    2015-01-01

    Rationale: Tools that screen inpatients for sepsis use the systemic inflammatory response syndrome (SIRS) criteria and organ dysfunctions, but most studies of these criteria were performed in intensive care unit or emergency room populations. Objectives: To determine the incidence and prognostic value of SIRS and organ dysfunctions in a multicenter dataset of hospitalized ward patients. Methods: Hospitalized ward patients at five hospitals from November 2008 to January 2013 were included. SIRS and organ system dysfunctions were defined using 2001 International Consensus criteria. Patient characteristics and in-hospital mortality were compared among patients meeting two or more SIRS criteria and by the presence or absence of organ system dysfunction. Measurements and Main Results: A total of 269,951 patients were included in the study, after excluding 48 patients with missing discharge status. Forty-seven percent (n = 125,841) of the included patients met two or more SIRS criteria at least once during their ward stay. On ward admission, 39,105 (14.5%) patients met two or more SIRS criteria, and patients presenting with SIRS had higher in-hospital mortality than those without SIRS (4.3% vs. 1.2%; P < 0.001). Fourteen percent of patients (n = 36,767) had at least one organ dysfunction at ward admission, and those presenting with organ dysfunction had increased mortality compared with those without organ dysfunction (5.3% vs. 1.1%; P < 0.001). Conclusions: Almost half of patients hospitalized on the wards developed SIRS at least once during their ward stay. Our findings suggest that screening ward patients using SIRS criteria for identifying those with sepsis would be impractical. PMID:26158402

  5. Acute restraint stress induces endothelial dysfunction: role of vasoconstrictor prostanoids and oxidative stress.

    PubMed

    Carda, Ana P P; Marchi, Katia C; Rizzi, Elen; Mecawi, André S; Antunes-Rodrigues, José; Padovan, Claudia M; Tirapelli, Carlos R

    2015-01-01

    We hypothesized that acute stress would induce endothelial dysfunction. Male Wistar rats were restrained for 2 h within wire mesh. Functional and biochemical analyses were conducted 24 h after the 2-h period of restraint. Stressed rats showed decreased exploration on the open arms of an elevated-plus maze (EPM) and increased plasma corticosterone concentration. Acute restraint stress did not alter systolic blood pressure, whereas it increased the in vitro contractile response to phenylephrine and serotonin in endothelium-intact rat aortas. NG-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase, NOS, inhibitor) did not alter the contraction induced by phenylephrine in aortic rings from stressed rats. Tiron, indomethacin and SQ29548 reversed the increase in the contractile response to phenylephrine induced by restraint stress. Increased systemic and vascular oxidative stress was evident in stressed rats. Restraint stress decreased plasma and vascular nitrate/nitrite (NOx) concentration and increased aortic expression of inducible (i) NOS, but not endothelial (e) NOS. Reduced expression of cyclooxygenase (COX)-1, but not COX-2, was observed in aortas from stressed rats. Restraint stress increased thromboxane (TX)B(2) (stable TXA(2) metabolite) concentration but did not affect prostaglandin (PG)F2α concentration in the aorta. Restraint reduced superoxide dismutase (SOD) activity, whereas concentrations of hydrogen peroxide (H(2)O(2)) and reduced glutathione (GSH) were not affected. The major new finding of our study is that restraint stress increases vascular contraction by an endothelium-dependent mechanism that involves increased oxidative stress and the generation of COX-derived vasoconstrictor prostanoids. Such stress-induced endothelial dysfunction could predispose to the development of cardiovascular diseases.

  6. Acute exposure of Drosophila melanogaster to paraquat causes oxidative stress and mitochondrial dysfunction.

    PubMed

    Hosamani, Ravikumar

    2013-05-01

    Paraquat (PQ; 1, 1'-dimethyl-4-4'-bipyridinium), an herbicide and model neurotoxicant, is identified to be one of the prime risk factors in Parkinson's disease (PD). In the Drosophila system, PQ is commonly used to measure acquired resistance against oxidative stress (PQ resistance test). Despite this, under acute PQ exposure, data on the oxidative stress response and associated impact on mitochondria among flies is limited. Accordingly, in this study, we measured markers of oxidative stress and mitochondrial dysfunctions among adult male flies (8-10 days old) exposed to varying concentrations of PQ (10, 20, and 40 mM in 5% sucrose solution) employing a conventional filter disc method for 24 h. PQ exposure resulted in significant elevation in the levels of oxidative stress biomarkers (malondialdehyde: 43% increase: hydroperoxide: 32-39% increase), with concomitant enhancement in reduced glutathione and total thiol levels in cytosol. Higher activity of antioxidant enzymes were also evident along with increased free iron levels. Furthermore, PQ exposure caused a concentration-dependent increase in mitochondrial superoxide generation and activity of manganese-superoxide dismutase (Mn-SOD). The activity levels of complex I-III, complex II-III, and Mg+2 adinosine triphosphatase (ATPase) were also decreased significantly. A robust diminution in the activity of succinate dehydrogenase and moderate decline in the citrate synthase activity suggested a specific effect on citric acid cycle enzymes. Collectively, these data suggest that acute PQ exposure causes significant oxidative stress and mitochondrial dysfunction among flies in vivo. It is suggested that in various experimental settings, while conducting the "PQ resistance stress test" incorporation of selected biochemical end points is likely to enhance the quality of the data.

  7. Isolated and persistent cognitive dysfunction in a patient with acute disseminated encephalomyelitis.

    PubMed

    Adamec, Ivan; Klepac, Nataša; Kolenc, Danijela; Ozretić, David; Habek, Mario

    2013-03-01

    We report a case of pathology-proven acute disseminated encephalomyelitis (ADEM) in which the patient's symptoms were solely cognitive. Although cognitive dysfunction is a well-recognized symptom in adults with multiple sclerosis, cognitive assessment of adults with ADEM has rarely been reported. A 35-year-old woman was referred to our center for evaluation of cognitive disturbance and demyelinating lesions seen on brain magnetic resonance imaging (MRI). We performed a neurologic examination, full neuropsychological assessment, brain MRI, blood and cerebrospinal fluid analyses, visual evoked potentials, and brain biopsy. The patient's Mini-Mental State Examination score was 26/30. Cognitive assessment revealed multiple severe dysfunctions, mainly in executive and attention tasks. She scored below the normal range on the Digit Span Forward and Backward Test and the Trail Making Test Part B. The Frontal Assessment Battery showed deficits in mental flexibility, motor programming, and inhibitory control. She also scored in the impaired range on tests of verbal fluency and memory. The brain MRI and biopsy confirmed a diagnosis of ADEM. This case report points to the limitations of relying on clinical presentation, neuroimaging, and current controversial diagnostic criteria in diagnosing ADEM in adults, and highlights the essential role of pathologic evaluation.

  8. Acute O-GlcNAcylation prevents inflammation-induced vascular dysfunction

    PubMed Central

    Hilgers, Rob H. P.; Xing, Dongqi; Gong, Kaizheng; Chen, Yiu-Fai; Chatham, John C.

    2012-01-01

    Acute increases in cellular protein O-linked N-acetyl-glucosamine (O-GlcNAc) modification (O-GlcNAcylation) have been shown to have protective effects in the heart and vasculature. We hypothesized that d-glucosamine (d-GlcN) and Thiamet-G, two agents that increase protein O-GlcNAcylation via different mechanisms, inhibit TNF-α-induced oxidative stress and vascular dysfunction by suppressing inducible nitric oxide (NO) synthase (iNOS) expression. Rat aortic rings were incubated for 3h at 37°C with d-GlcN or its osmotic control l-glucose (l-Glc) or with Thiamet-G or its vehicle control (H2O) followed by the addition of TNF-α or vehicle (H2O) for 21 h. After incubation, rings were mounted in a myograph to assess arterial reactivity. Twenty-four hours of incubation of aortic rings with TNF-α resulted in 1) a hypocontractility to 60 mM K+ solution and phenylephrine, 2) blunted endothelium-dependent relaxation responses to ACh and substance P, and 3) unaltered relaxing response to the Ca2+ ionophore A-23187 and the NO donor sodium nitroprusside compared with aortic rings cultured in the absence of TNF-α. d-GlcN and Thiamet-G pretreatment suppressed the TNF-α-induced hypocontractility and endothelial dysfunction. Total protein O-GlcNAc levels were significantly higher in aortic segments treated with d-GlcN or Thiamet-G compared with controls. Expression of iNOS protein was increased in TNF-α-treated rings, and this was attenuated by pretreatment with either d-GlcN or Thiamet-G. Dense immunostaining for nitrotyrosylated proteins was detected in the endothelium and media of the aortic wall, suggesting enhanced peroxynitrite production by iNOS. These findings demonstrate that acute increases in protein O-GlcNAcylation prevent TNF-α-induced vascular dysfunction, at least in part, via suppression of iNOS expression. PMID:22777418

  9. Urinary mitochondrial DNA is a biomarker of mitochondrial disruption and renal dysfunction in acute kidney injury

    PubMed Central

    Whitaker, Ryan M.; Stallons, L. Jay; Kneff, Joshua E.; Alge, Joseph L.; Harmon, Jennifer L.; Rahn, Jennifer J.; Arthur, John M.; Beeson, Craig C.; Chan, Sherine L.; Schnellmann, Rick G.

    2015-01-01

    Recent studies show the importance of mitochondrial dysfunction in the initiation and progression of acute kidney injury (AKI). However, no biomarkers exist linking renal injury to mitochondrial function and integrity. To this end, we evaluated urinary mitochondrial DNA (UmtDNA) as a biomarker of renal injury and function in humans with AKI following cardiac surgery. mtDNA was isolated from the urine of patients following cardiac surgery and quantified by qPCR. Patients were stratified into no AKI, stable AKI and progressive AKI groups based on Acute Kidney Injury Network (AKIN) staging. UmtDNA was elevated in progressive AKI patients, and was associated with progression of patients with AKI at collection to higher AKIN stages. To evaluate the relationship of UmtDNA to measures of renal mitochondrial integrity in AKI, mice were subjected to sham surgery or varying degrees of ischemia followed by 24 hours of reperfusion. UmtDNA increased in mice after 10-15 minutes of ischemia and positively correlated with ischemia time. Furthermore, UmtDNA was predictive of AKI in the mouse model. Finally, UmtDNA levels were negatively correlated with renal cortical mtDNA and mitochondrial gene expression. These translational studies demonstrate that UmtDNA is associated with recovery from AKI following cardiac surgery by serving as an indicator of mitochondrial integrity. Thus, UmtDNA may serve as valuable biomarker for the development of mitochondrial targeted therapies in AKI. PMID:26287315

  10. Risk Factors for Multiple Organ Dysfunction Syndrome in Severe Stroke Patients

    PubMed Central

    Yang, Shuna; Li, Yue; Yuan, Junliang; Yang, Lei; Li, Shujuan; Hu, Wenli

    2016-01-01

    Background Severe stroke patients have poor clinical outcome which may be associated with development of multiple organ dysfunction syndrome (MODS). Therefore, the aim of our study was to investigate independent risk factors for development of MODS in severe stroke patients. Methods Ninety seven severe stroke patients were prospective recruited from Jan 2011 to Jun 2015. The development of MODS was identified by Sequential Organ Failure Assessment (SOFA) score (score ≥ 3, at least two organs), which was assessed on day 1, 4, 7, 10 and 14 after admission. Baseline characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow coma score (GCS) and cerebral imaging parameters were collected at admission. Cox regression was performed to determine predictors for the development of MODS. Medical complications after admission and in-hospital mortality were also investigated. Results 33 (34%) patients were in MODS group and 64 (66%) were in non-MODS group within 14 days after admission. Patients in MODS group had more smoker (51.5% vs 28.1%, p = 0.023), higher NIHSS score (23.48 ± 6.12 vs 19.81 ± 4.83, p = 0.004), higher APACHE II score (18.70 ± 5.18 vs 15.64 ± 4.36, p = 0.003) and lower GCS score (6.33 ± 2.48 vs 8.14 ± 2.73, p = 0.002). They also had higher rate of infarction in multi vascular territories (36.4% vs 10.9%, p = 0.003). The most common complication in all patients was pulmonary infection, while complication scores were comparable between two groups. Patients with MODS had higher in-hospital mortality (69.7% vs 9.4%, p = 0.000). In Cox regression, NIHSS score (RR = 1.084, 95% CI 1.019–1.153) and infarction in multi vascular territories (RR = 2.345 95% CI 1.105–4.978) were independent risk factors for development of MODS. Conclusions In acute phase of stroke, NIHSS score and infarction in multi vascular territories predicted MODS in severe stroke patients. Moreover, patients with MODS had higher in-hospital mortality

  11. Organ failure associated with acute pancreatitis in African-American and Hispanic patients.

    PubMed Central

    Shaheen, Magda A.; Akhtar, Abbasi J.

    2007-01-01

    OBJECTIVE: We studied the relationship between acute pancreatitis and organ failure in African-American and Hispanic patients. METHODS: The medical records of 760 (417 African-American and 343 Hispanic) patients aged 19-85 years diagnosed with acute pancreatitis over 15 years were reviewed retrospectively. We abstracted and analyzed data related to demographics, etiology, type of pancreatitis, organ failure and mortality. RESULTS: Of the 760 patients, 24% had organ failure. Of the 182 patients with organ failure, 125 patients (69%) had multiple organ failure, whereas 57 patients (31%) had single type. Cardiovascular system failure was the common organ dysfunction (28%). Of the 760 patients, 14% died. Patients with organ failure had a higher mortality (40%) compared with those without it (6%) (OR=9.6, 95% CI: 6.0-15.3) (P=0.001). Mortality was higher among those with multiple organ failure (46%) compared with those with single type (25%). Mortality was highest among those with pulmonary failure (57%). CONCLUSION: The prevalence of organ failure in our study was slightly higher than the general population (20%). Mortality from single type was higher than that reported in previous studies (8-11%), especially mortality from pulmonary failure (18%). Prevention, early diagnosis and prompt treatment of organ failure may improve the clinical outcome. PMID:18229777

  12. Multi-organ autonomic dysfunction in Parkinson disease

    PubMed Central

    2010-01-01

    Both pathologic and clinical studies of autonomic pathways have expanded the concept of Parkinson disease (PD) from a movement disorder to a multi-level widespread neurodegenerative process with non-motor features spanning several organ systems. This review integrates neuropathologic findings and autonomic physiology in PD as it relates to end organ autonomic function. Symptoms, pathology and physiology of the cardiovascular, skin/sweat gland, urinary, gastrointestinal, pupillary and neuroendocrine systems can be probed by autopsy, biopsy and non-invasive electrophysiological techniques in vivo which assess autonomic anatomy and function. There is mounting evidence that PD affects a chain of neurons in autonomic pathways. Consequently, autonomic physiology may serve as a window into non-motor PD progression and allow the development of mechanistically based treatment strategies for several non-motor features of PD. End-organ physiologic markers may be used to inform a model of PD pathophysiology and non-motor progression. PMID:20851033

  13. [Effect of angioprotective therapy with bioflavonoids on endothelial dysfunction in patients with acute venous thromboses].

    PubMed

    Bryushkov, A Yu; Ershov, P V; Sergeeva, N A; Bogachev, V Yu

    The study was aimed at evaluating a possibility of correcting endothelial dysfunction by means of angioprotective therapy with natural-origin bioflavonoids in patients presenting with acute venous thromboses. Ours was an open comparative prospective study including a total of thirty 34-to-60-year-old patients suffering from lower limb deep vein thrombosis. The patients were subdivided into two groups. The Study Group was composed of 15 patients receiving on the background of anticoagulant therapy with direct thrombin inhibitors (dabigatran etexilate at a daily dose of 300 mg) natural-origin angioprotectors (red grape leaf extract). The Control Group also consisted of 15 patients undergoing anticoagulant therapy with direct thrombin inhibitors alone. Blood sampling for laboratory monitoring [the quantitative level of von Willebrand factor (vWF) in blood plasma, integral assessment of the links of blood coagulation and fibrinolysis by means of thromboelastography] and ultrasonographic angioscanning of lower extremities were carried out in both Group twice: at the beginning of the study and 3 months after the beginning of therapy. The absolute majority of patients demonstrated a quantitative increase in vWF (the median in the Study Group amounted to 208.3%, being 190.0% in the Control Group, with the cut-off level equaling 140.8%). Assessing dynamics of the vWF level after 3 months on the background of using natural-origin flavonoids (the Study Group) showed a more pronounced decrease in the vWF level in the Study Group patients as compared with the Control Group patients (98.4%). Comparing the dynamic composite indices of the thromboelastogram revealed that with similar parameters in patients from the Study and Control Groups at admission, in dynamics there was observed greater growth of the level of indices of the process of dissolution of the fibrin clot (lysis) in the Study Group as compared to the Control Group. Also noted was more pronounced recanalization of

  14. Background Noise Contributes to Organic Solvent Induced Brain Dysfunction

    PubMed Central

    Guthrie, O'neil W.; Wong, Brian A.; McInturf, Shawn M.; Reboulet, James E.; Ortiz, Pedro A.; Mattie, David R.

    2016-01-01

    Occupational exposure to complex blends of organic solvents is believed to alter brain functions among workers. However, work environments that contain organic solvents are also polluted with background noise which raises the issue of whether or not the noise contributed to brain alterations. The purpose of the current study was to determine whether or not repeated exposure to low intensity noise with and without exposure to a complex blend of organic solvents would alter brain activity. Female Fischer344 rats served as subjects in these experiments. Asynchronous volume conductance between the midbrain and cortex was evaluated with a slow vertex recording technique. Subtoxic solvent exposure, by itself, had no statistically significant effects. However, background noise significantly suppressed brain activity and this suppression was exacerbated with solvent exposure. Furthermore, combined exposure produced significantly slow neurotransmission. These abnormal neurophysiologic findings occurred in the absence of hearing loss and detectable damage to sensory cells. The observations from the current experiment raise concern for all occupations where workers are repeatedly exposed to background noise or noise combined with organic solvents. Noise levels and solvent concentrations that are currently considered safe may not actually be safe and existing safety regulations have failed to recognize the neurotoxic potential of combined exposures. PMID:26885406

  15. Pituitary dysfunction in traumatic brain injury: Is evaluation in the acute phase worthwhile?

    PubMed Central

    Dalwadi, Pradip P.; Bhagwat, Nikhil M.; Tayde, Parimal S.; Joshi, Ameya S.; Varthakavi, Premlata K.

    2017-01-01

    Introduction: Traumatic brain injury (TBI) is an under-recognized cause of hypopituitarism. According to recent data, it could be more frequent than previously known. However, there is a scarcity of data in Indian population. Aims: The main aim of the study was to determine the prevalence of pituitary hormone deficiencies in the acute phase of TBI. The secondary objectives were to correlate the severity of trauma with basal hormone levels and to determine whether initial hormone deficiencies predict mortality. Subjects and Methods: Forty-nine TBI patients (41 men and 8 women) were included in this study. Pituitary functions were evaluated within 24 h of admission. Results: Gonadotropin deficiency was found in 65.3% patient while 46.9% had low insulin-like growth factor-1, 12.24% had cortisol level <7 mcg/dl. Cortisol and prolactin level were positively correlated with the severity of TBI suggestive of stress response. Free triiodothyronine (fT3) and free thyroxine were significantly lower in patients with increasing severity of tuberculosis. Logistic regression analysis revealed that mortality after TBI was unrelated to the basal pituitary hormone levels except low T3 level, which was found to be positively related to mortality. Conclusions: Pituitary dysfunction is common after TBI and the most commonly affected axes are growth hormone and gonadotropin axis. Low fT3 correlates best with mortality. During the acute phase of TBI, at least an assessment of cortisol is vital as undetected cortisol deficiency can be life-threatening PMID:28217503

  16. Longitudinal characterization of dysfunctional T cell-activation during human acute Ebola infection.

    PubMed

    Agrati, C; Castilletti, C; Casetti, R; Sacchi, A; Falasca, L; Turchi, F; Tumino, N; Bordoni, V; Cimini, E; Viola, D; Lalle, E; Bordi, L; Lanini, S; Martini, F; Nicastri, E; Petrosillo, N; Puro, V; Piacentini, M; Di Caro, A; Kobinger, G P; Zumla, A; Ippolito, G; Capobianchi, M R

    2016-03-31

    Data on immune responses during human Ebola virus disease (EVD) are scanty, due to limitations imposed by biosafety requirements and logistics. A sustained activation of T-cells was recently described but functional studies during the acute phase of human EVD are still missing. Aim of this work was to evaluate the kinetics and functionality of T-cell subsets, as well as the expression of activation, autophagy, apoptosis and exhaustion markers during the acute phase of EVD until recovery. Two EVD patients admitted to the Italian National Institute for Infectious Diseases, Lazzaro Spallanzani, were sampled sequentially from soon after symptom onset until recovery and analyzed by flow cytometry and ELISpot assay. An early and sustained decrease of CD4 T-cells was seen in both patients, with an inversion of the CD4/CD8 ratio that was reverted during the recovery period. In parallel with the CD4 T-cell depletion, a massive T-cell activation occurred and was associated with autophagic/apoptotic phenotype, enhanced expression of the exhaustion marker PD-1 and impaired IFN-gamma production. The immunological impairment was accompanied by EBV reactivation. The association of an early and sustained dysfunctional T-cell activation in parallel to an overall CD4 T-cell decline may represent a previously unknown critical point of Ebola virus (EBOV)-induced immune subversion. The recent observation of late occurrence of EBOV-associated neurological disease highlights the importance to monitor the immuno-competence recovery at discharge as a tool to evaluate the risk of late sequelae associated with resumption of EBOV replication. Further studies are required to define the molecular mechanisms of EVD-driven activation/exhaustion and depletion of T-cells.

  17. Longitudinal characterization of dysfunctional T cell-activation during human acute Ebola infection

    PubMed Central

    Agrati, C; Castilletti, C; Casetti, R; Sacchi, A; Falasca, L; Turchi, F; Tumino, N; Bordoni, V; Cimini, E; Viola, D; Lalle, E; Bordi, L; Lanini, S; Martini, F; Nicastri, E; Petrosillo, N; Puro, V; Piacentini, M; Di Caro, A; Kobinger, G P; Zumla, A; Ippolito, G; Capobianchi, M R

    2016-01-01

    Data on immune responses during human Ebola virus disease (EVD) are scanty, due to limitations imposed by biosafety requirements and logistics. A sustained activation of T-cells was recently described but functional studies during the acute phase of human EVD are still missing. Aim of this work was to evaluate the kinetics and functionality of T-cell subsets, as well as the expression of activation, autophagy, apoptosis and exhaustion markers during the acute phase of EVD until recovery. Two EVD patients admitted to the Italian National Institute for Infectious Diseases, Lazzaro Spallanzani, were sampled sequentially from soon after symptom onset until recovery and analyzed by flow cytometry and ELISpot assay. An early and sustained decrease of CD4 T-cells was seen in both patients, with an inversion of the CD4/CD8 ratio that was reverted during the recovery period. In parallel with the CD4 T-cell depletion, a massive T-cell activation occurred and was associated with autophagic/apoptotic phenotype, enhanced expression of the exhaustion marker PD-1 and impaired IFN-gamma production. The immunological impairment was accompanied by EBV reactivation. The association of an early and sustained dysfunctional T-cell activation in parallel to an overall CD4 T-cell decline may represent a previously unknown critical point of Ebola virus (EBOV)-induced immune subversion. The recent observation of late occurrence of EBOV-associated neurological disease highlights the importance to monitor the immuno-competence recovery at discharge as a tool to evaluate the risk of late sequelae associated with resumption of EBOV replication. Further studies are required to define the molecular mechanisms of EVD-driven activation/exhaustion and depletion of T-cells. PMID:27031961

  18. Visually Guided Hand Movements in Children with Minor Neurological Dysfunction: Response Time and Movement Organization.

    ERIC Educational Resources Information Center

    Schellekens, J. M. H.; And Others

    1983-01-01

    Presents preliminary data on how, during the execution of visually guided hand movements, differences in response time between children with and without signs of minor neurological dysfunction may be related to differences in the spatio-temporal organization of their movements. (MP)

  19. Multiple Organ Dysfunction Score Is Superior to the Obstetric-Specific Sepsis in Obstetrics Score in Predicting Mortality in Septic Obstetric Patients

    PubMed Central

    Ryan, Helen M.; Magee, Laura A.; von Dadelszen, Peter; Fjell, Chris; Walley, Keith R.

    2017-01-01

    Objectives: Mortality prediction scores have been used for a long time in ICUs; however, numerous studies have shown that they over-predict mortality in the obstetric population. With sepsis remaining a major cause of obstetric mortality, we aimed to look at five mortality prediction scores (one obstetric-based and four general) in the septic obstetric population and compare them to a nonobstetric septic control group. Subject and Design: Women in the age group of 16–50 years with an admission diagnosis or suspicion of sepsis were included. In a multicenter obstetric population (n = 797), these included all pregnant and postpartum patients up to 6 weeks postpartum. An age- and gender-matched control nonobstetric population was drawn from a single-center general critical care population (n = 2,461). Sepsis in Obstetric Score, Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment, and Multiple Organ Dysfunction Scores were all applied to patients meeting inclusion criteria in both cohorts, and their area under the receiver-operator characteristic curves was calculated to find the most accurate predictor. Measurements and Main Results: A total of 146 septic patients were found for the obstetric cohort and 299 patients for the nonobstetric control cohort. The Sepsis in Obstetric Score, Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment, and Multiple Organ Dysfunction Scores gave area under the receiver-operator characteristic curves of 0.67, 0.68, 0.72, 0.79, and 0.84 in the obstetric cohort, respectively, and 0.64, 0.72, 0.61, 0.78, and 0.74 in the nonobstetric cohort, respectively. The Sepsis in Obstetric Score performed similarly to all the other scores with the exception of the Multiple Organ Dysfunction Score, which was significantly better (p < 0.05). Conclusion: The Sepsis in Obstetric Score, designed specifically for

  20. Differences in organ dysfunctions between neonates and older children: a prospective, observational, multicenter study

    PubMed Central

    2010-01-01

    Introduction The multiple organ dysfunction syndrome (MODS) is a major cause of death for patients admitted to pediatric intensive care units (PICU). The Pediatric Logistic Organ Dysfunction (PELOD) score has been validated in order to describe and quantify the severity of organ dysfunction (OD). There are several physiological differences between neonates and older children. The objective of the study was to determine whether there are differences in incidence of ODs and mortality rate between full-term neonates (age <28 days) and older children. Methods In a prospective, observational study, 1806 patients, admitted to seven PICUs between September 1998 and February 2000 were included. The PELOD score, which includes six organ dysfunctions and 12 variables, was recorded daily. For each variable, the most abnormal value was used to define the daily OD. For each OD, the most abnormal value each day and that during the entire stay were used in calculating the daily PELOD and PELOD scores, respectively. The relationships between OD, daily OD, PELOD, daily PELOD and mortality were compared between the two strata (neonates, older children) based on the discrimination power, logistic and multiple regression analyses. Results Of the 1806 enrolled patients 171 (9.5%) were neonates. Incidence of MODS and mortality rate were higher among neonates than in older children (14.6% vs. 5.5%, P < 10-7; 75.4%, vs. 50.9%, P < 10-4; respectively). Daily PELOD scores were significantly higher in neonates from day 1 to day 4. Daily cardiovascular, respiratory and renal dysfunction scores from day 1 to day 4 as well as the PELOD score for the entire pediatric intensive care unit stay were also significantly higher in neonates. Neurological, cardiovascular, and hepatic dysfunctions were independent predictors of death among neonates while all ODs significantly contributed to the risk of mortality in older children. Conclusions Our data demonstrate that incidence of MODS and mortality rate

  1. Acute Alcohol Intoxication Prolongs Neuroinflammation without Exacerbating Neurobehavioral Dysfunction following Mild Traumatic Brain Injury

    PubMed Central

    Teng, Sophie X.

    2014-01-01

    Abstract Traumatic brain injury (TBI) represents a leading cause of death and disability among young persons with ∼1.7 million reported cases in the United States annually. Although acute alcohol intoxication (AAI) is frequently present at the time of TBI, conflicting animal and clinical reports have failed to establish whether AAI significantly impacts short-term outcomes after TBI. The objective of this study was to determine whether AAI at the time of TBI aggravates neurobehavioral outcomes and neuroinflammatory sequelae post-TBI. Adult male Sprague-Dawley rats were surgically instrumented with gastric and vascular catheters before a left lateral craniotomy. After recovery, rats received either a primed constant intragastric alcohol infusion (2.5 g/kg+0.3 g/kg/h for 15 h) or isocaloric/isovolumic dextrose infusion followed by a lateral fluid percussion TBI (∼1.4 J, ∼30 ms). TBI induced apnea and a delay in righting reflex. AAI at the time of injury increased the TBI induced delay in righting reflex without altering apnea duration. Neurological and behavioral dysfunction was observed at 6 h and 24 h post-TBI, and this was not exacerbated by AAI. TBI induced a transient upregulation of cortical interleukin (IL)-6 and monocyte chemotactic protein (MCP)-1 mRNA expression at 6 h, which was resolved at 24 h. AAI did not modulate the inflammatory response at 6 h but prevented resolution of inflammation (IL-1, IL-6, tumor necrosis factor-α, and MCP-1 expression) at 24 h post-TBI. AAI at the time of TBI did not delay the recovery of neurological and neurobehavioral function but prevented the resolution of neuroinflammation post-TBI. PMID:24050411

  2. Procainamide Inhibits DNA Methylation and Alleviates Multiple Organ Dysfunction in Rats with Endotoxic Shock

    PubMed Central

    Shih, Chih-Chin; Liao, Mei-Hui; Hsiao, Tsan-Seng; Hii, Hiong-Ping; Shen, Ching-Hui; Chen, Shiu-Jen; Ka, Shuk-Man; Chang, Yung-Lung; Wu, Chin-Chen

    2016-01-01

    Excessive inflammatory and oxidative stress lead to circulatory failure, multiple organ dysfunction, and high mortality in patients with sepsis. Microbial infection-induced DNA hypermethylation is associated with the augmentation of inflammation and oxidative stress. In our previous study, the antiarrhythmic drug procainamide inhibits the expression of DNA methyltransferase 1 (DNMT1) and diminishes IL-6 levels in rats with rhabdomyolysis. Thus, we further evaluated the effects of procainamide on the development of circulatory failure and multiple organ dysfunction in rats with endotoxic shock. Male Wistar rats were intravenously infused with saline or lipopolysaccharide (LPS) followed by procainamide administration. The changes of hemodynamics, blood glucose, biochemical variables, and plasma nitric oxide (NO) levels were analyzed during the experimental period. At the end of experiments, animal organs were also obtained for examining superoxide production, neutrophil infiltration, and DNA methylation status. Our results showed that LPS induced circulatory failure, multiple organ dysfunction, and high mortality rate in endotoxemic rats. Overt neutrophil infiltration and superoxide production, accompanied by the elevations of DNMT1 and 5-methylcytosine levels in the lung of endotoxemic rats were also observed. Treatment of endotoxemic animals with procainamide not only inhibited the increased levels of DNMT1 and 5-methylcytosine but also ameliorated neutrophil infiltration and superoxide production in the lung. In addition, the anti-inflammatory gene, IL27RA, was down-regulated in the LPS group and up-regulated in the LPS + Procainamide group. Procainamide also diminished IL27RA methylation in the lung of endotoxemic rat. Moreover, both DNMT inhibitors procainamide and hydralazine improved hypotension, hypoglycemia, and multiple organ dysfunction of LPS-treated rats. Thus, we suggest that the beneficial effects of procainamide could be attributed to the suppression

  3. Concomitant Impact of High-Sensitivity C-Reactive Protein and Renal Dysfunction in Patients with Acute Myocardial Infarction

    PubMed Central

    Kang, Yong Un; Kim, Min Jee; Choi, Joon Seok; Kim, Chang Seong; Bae, Eun Hui; Ma, Seong Kwon; Ahn, Young-Keun; Jeong, Myung Ho; Kim, Young Jo; Cho, Myeong Chan; Kim, Chong Jin

    2014-01-01

    Purpose The present study aimed to investigate the impact of high-sensitivity C-reactive protein (hs-CRP) and renal dysfunction on clinical outcomes in acute myocardial infarction (AMI) patients. Materials and Methods The study involved a retrospective cohort of 8332 patients admitted with AMI. The participants were divided into 4 groups according to the levels of estimated glomerular filtration rate (eGFR) and hs-CRP: group I, no renal dysfunction (eGFR ≥60 mL·min-1·1.73 m-2) with low hs-CRP (≤2.0 mg/dL); group II, no renal dysfunction with high hs-CRP; group III, renal dysfunction with low hs-CRP; and group IV, renal dysfunction with high hs-CRP. We compared major adverse cardiac events (MACE) over a 1-year follow-up period. Results The 4 groups demonstrated a graded association with increased MACE rates (group I, 8.8%; group II, 13.8%; group III, 18.6%; group IV, 30.1%; p<0.001). In a Cox proportional hazards model, mortality at 12 months increased in groups II, III, and IV compared with group I [hazard ratio (HR) 2.038, 95% confidence interval (CI) 1.450-2.863, p<0.001; HR 3.003, 95% CI 2.269-3.974, p<0.001; HR 5.087, 95% CI 3.755-6.891, p<0.001]. Conclusion High hs-CRP, especially in association with renal dysfunction, is related to the occurrence of composite MACE, and indicates poor prognosis in AMI patients. PMID:24339298

  4. Cognitive dysfunction correlates with elevated serum S100B concentration in drug-free acutely relapsed patients with schizophrenia.

    PubMed

    Chen, Song; Tian, Li; Chen, Nan; Xiu, Meihong; Wang, Zhiren; Yang, Guigang; Wang, Chuanyue; Yang, Fude; Tan, Yunlong

    2017-01-01

    S100B, a biomarker of glial dysfunction and blood-brain barrier (BBB) disruption, has been proposed to be involved in the pathophysiology of schizophrenia. In the present study, we aimed at exploring the association of serum S100B levels with cognitive deficits using MATRICS Consensus Cognitive Battery (MCCB) in schizophrenia, by excluding the impact of antipsychotics. Sixty-two unmedicated patients with schizophrenia during their acute phases were divided into a drug-naïve group (n=34) and a drug-free group (n=28). S100B serum concentrations were measured and MCCB was administered to all of the patients. Forty healthy controls donated their blood samples for S100B assessment. The results indicated that serum S100B was significantly elevated in the drug-naive/free acute-stage schizophrenic patients when compared to the healthy controls. In the drug-free group, the serum S100B level was an independent contributor to the global cognitive dysfunctions, particularly for the speed of processing, attention/vigilance, visual learning and reasoning/problem solving subscores. Nevertheless, no significant associations between S100B and MCCB composite score or any cognitive domain subscore were observed in the drug-naïve group. These findings support the hypothesis that glial dysfunction and associated marker protein S100B may contribute to the pathophysiologic development of neurocognitive deficits in the relapsed individuals with schizophrenia.

  5. An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical Presentation

    PubMed Central

    Pena, Olga M.; Hancock, David G.; Lyle, Ngan H.; Linder, Adam; Russell, James A.; Xia, Jianguo; Fjell, Christopher D.; Boyd, John H.; Hancock, Robert E.W.

    2014-01-01

    Background Sepsis involves aberrant immune responses to infection, but the exact nature of this immune dysfunction remains poorly defined. Bacterial endotoxins like lipopolysaccharide (LPS) are potent inducers of inflammation, which has been associated with the pathophysiology of sepsis, but repeated exposure can also induce a suppressive effect known as endotoxin tolerance or cellular reprogramming. It has been proposed that endotoxin tolerance might be associated with the immunosuppressive state that was primarily observed during late-stage sepsis. However, this relationship remains poorly characterised. Here we clarify the underlying mechanisms and timing of immune dysfunction in sepsis. Methods We defined a gene expression signature characteristic of endotoxin tolerance. Gene-set test approaches were used to correlate this signature with early sepsis, both newly and retrospectively analysing microarrays from 593 patients in 11 cohorts. Then we recruited a unique cohort of possible sepsis patients at first clinical presentation in an independent blinded controlled observational study to determine whether this signature was associated with the development of confirmed sepsis and organ dysfunction. Findings All sepsis patients presented an expression profile strongly associated with the endotoxin tolerance signature (p < 0.01; AUC 96.1%). Importantly, this signature further differentiated between suspected sepsis patients who did, or did not, go on to develop confirmed sepsis, and predicted the development of organ dysfunction. Interpretation Our data support an updated model of sepsis pathogenesis in which endotoxin tolerance-mediated immune dysfunction (cellular reprogramming) is present throughout the clinical course of disease and related to disease severity. Thus endotoxin tolerance might offer new insights guiding the development of new therapies and diagnostics for early sepsis. PMID:25685830

  6. Daily estimation of the severity of multiple organ dysfunction syndrome in critically ill children

    PubMed Central

    Leteurtre, Stéphane; Duhamel, Alain; Grandbastien, Bruno; Proulx, François; Cotting, Jacques; Gottesman, Ronald; Joffe, Ari; Wagner, Bendicht; Hubert, Philippe; Martinot, Alain; Lacroix, Jacques; Leclerc, Francis

    2010-01-01

    Background Daily evaluation of multiple organ dysfunction syndrome has been performed in critically ill adults. We evaluated the clinical course of multiple organ dysfunction over time in critically ill children using the Pediatric Logistic Organ Dysfunction (PELOD) score and determined the optimal days for measuring scores. Methods We prospectively measured daily PELOD scores and calculated the change in scores over time for 1806 consecutive patients admitted to seven pediatric intensive care units (PICUs) between September 1998 and February 2000. To study the relationship between daily scores and mortality in the PICU, we evaluated changes in daily scores during the first four days; the mean rate of change in scores during the entire PICU stay between survivors and nonsurvivors; and Cox survival analyses using a change in PELOD score as a time-dependent covariate to determine the optimal days for measuring daily scores. Results The overall mortality among the 1806 patients was 6.4%. A high PELOD score (≥ 20 points) on day 1 was associated with an odds ratio (OR) for death of 40.7 (95% confidence interval [CI] 20.3–81.4); a medium score (10–19 points) on day 1 was associated with an OR for death of 4.2 (95% CI 2.0–8.7). Mortality was 50% when a high score on day 1 increased on day 2. The course of daily PELOD scores differed between survivors and nonsurvivors. A set of seven days (days 1, 2, 5, 8, 12, 16 and 18) was identified as the optimal period for measurement of daily PELOD scores. Interpretation PELOD scores indicating a worsening condition or no improvement over time were indicators of a poor prognosis in the PICU. A set of seven days for measurement of the PELOD score during the PICU stay provided optimal information on the progression of multiple-organ dysfunction syndrome in critically ill children. PMID:20547715

  7. The Oxidative and Inflammatory State in Patients with Acute Renal Graft Dysfunction Treated with Tacrolimus

    PubMed Central

    Carrillo-Ibarra, Sandra; Cerrillos-Gutiérrez, José Ignacio; Escalante-Núñez, Ariadna; Rojas-Campos, Enrique; Gómez-Navarro, Benjamín; Sifuentes-Franco, Sonia

    2016-01-01

    Objective. To determine the oxidative stress/inflammation behavior in patients with/without acute graft dysfunction (AGD) with Tacrolimus. Methods. Cross-sectional study, in renal transplant (RT) recipients (1-yr follow-up). Patients with AGD and without AGD were included. Serum IL-6, TNF-α, 8-isoprostanes (8-IP), and Nitric Oxide (NO) were determined by ELISA; C-reactive protein (CRP) was determined by nephelometry; lipid peroxidation products (LPO) and superoxide dismutase (SOD) were determined by colorimetry. Results. The AGD presentation was at 5.09 ± 3.07 versus 8.27 ± 3.78 months (p < 0.001); CRP >3.19 mg/L was found in 21 versus 19 in the N-AGD group (p = 0.83); TNF-α 145.53 ± 18.87 pg/mL versus 125.54 ± 15.92 pg/mL in N-AGD (p = 0.64); IL-6 2110.69 ± 350.97 pg/mL versus 1933.42 ± 235.38 pg/mL in N-AGD (p = 0.13). The LPO were higher in AGD (p = 0.014): 4.10 ± 0.69 µM versus 2.41 ± 0.29 µM; also levels of 8-IP were higher in AGD 27.47 ± 9.28 pg/mL versus 8.64 ± 1.54 pg/mL (p = 0.01). Serum levels of NO in AGD were lower 138.44 ± 19.20 µmol/L versus 190.57 ± 22.04 µmol/L in N-AGD (p = 0.042); antioxidant enzyme SOD activity was significantly diminished in AGD with 9.75 ± 0.52 U/mL versus 11.69 ± 0.55 U/mL in N-AGD (p = 0.012). Discussion. Patients with RT present with a similar state of the proinflammatory cytokines whether or not they have AGD. The patients with AGD showed deregulation of the oxidative state with increased LPO and 8-IP and decreased NO and SOD. PMID:27872679

  8. Early Hepatic Dysfunction Is Associated with a Worse Outcome in Patients Presenting with Acute Respiratory Distress Syndrome: A Post-Hoc Analysis of the ACURASYS and PROSEVA Studies

    PubMed Central

    Dizier, Stéphanie; Forel, Jean-Marie; Ayzac, Louis; Richard, Jean-Christophe; Hraiech, Sami; Lehingue, Samuel; Loundou, Anderson; Roch, Antoine; Guerin, Claude; Papazian, Laurent

    2015-01-01

    Introduction Bilirubin is well-recognized marker of hepatic dysfunction in intensive care unit (ICU) patients. Multiple organ failure often complicates acute respiratory distress syndrome (ARDS) evolution and is associated with high mortality. The effect of early hepatic dysfunction on ARDS mortality has been poorly investigated. We evaluated the incidence and the prognostic significance of increased serum bilirubin levels in the initial phase of ARDS. Methods The data of 805 patients with ARDS were retrospectively analysed. This population was extracted from two recent multicenter, prospective and randomised trials. Patients presenting with ARDS with a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen < 150 mmHg measured with a PEEP ≥ 5 cm of water were included. The total serum bilirubin was measured at inclusion and at days 2, 4, 7 and 14. The primary objective was to analyse the bilirubin at inclusion according to the 90-day mortality rate. Results The 90-day mortality rate was 33.8% (n = 272). The non-survivors were older, had higher Sepsis-related Organ Failure Assessment (SOFA) score and were more likely to have a medical diagnosis on admission than the survivors. At inclusion, the SOFA score without the liver score (10.3±2.9 vs. 9.0±3.0, p<0.0001) and the serum bilirubin levels (36.1±57.0 vs. 20.5±31.5 μmol/L, p<0.0001) were significantly higher in the non-survivors than in the survivors. Age, the hepatic SOFA score, the coagulation SOFA score, the arterial pH level, and the plateau pressure were independently associated with 90-day mortality in patients with ARDS. Conclusion Bilirubin used as a surrogate marker of hepatic dysfunction and measured early in the course of ARDS was associated with the 90-day mortality rate. PMID:26636318

  9. The role of mitochondrial dysfunction in sepsis-induced multi-organ failure

    PubMed Central

    Singer, Mervyn

    2014-01-01

    An important role for bioenergetic dysfunction is increasingly emerging to potentially explain the paradox of clinical and biochemical organ failure in sepsis yet minimal cell death, maintained tissue oxygenation and recovery in survivors. Associations are well-recognized between the degree of mitochondrial dysfunction and outcomes. While this does not confirm cause-and-effect, it does nevertheless suggest a new route for therapeutic intervention focused on either mitochondrial protection or acceleration of the recovery process through stimulation of mitochondrial biogenesis (new protein turnover). This is particularly pertinent in light of the multiple trial failures related to immunomodulatory therapies. This overview will provide insights into mitochondrial biology, the relevance to sepsis, and therapeutic opportunities that possibly emerge. PMID:24185508

  10. Silent left ventricular dysfunction during routine activity after thrombolytic therapy for acute myocardial infarction

    SciTech Connect

    Kayden, D.S.; Wackers, F.J.; Zaret, B.L. )

    1990-06-01

    To investigate prospectively the occurrence and significance of postinfarction transient left ventricular dysfunction, 33 ambulatory patients who underwent thrombolytic therapy after myocardial infarction were monitored continuously for 187 +/- 56 min during normal activity with a radionuclide left ventricular function detector at the time of hospital discharge. Twelve patients demonstrated 19 episodes of transient left ventricular dysfunction (greater than 0.05 decrease in ejection fraction, lasting greater than or equal to 1 min), with no change in heart rate. Only two episodes in one patient were associated with chest pain and electrocardiographic changes. The baseline ejection fraction was 0.52 +/- 0.12 in patients with transient left ventricular dysfunction and 0.51 +/- 0.13 in patients without dysfunction (p = NS). At follow-up study (19.2 +/- 5.4 months), cardiac events (unstable angina, myocardial infarction or death) occurred in 8 of 12 patients with but in only 3 of 21 patients without transient left ventricular dysfunction (p less than 0.01). During submaximal supine bicycle exercise, only two patients demonstrated a decrease in ejection fraction greater than or equal to 0.05 at peak exercise; neither had a subsequent cardiac event. These data suggest that transient episodes of silent left ventricular dysfunction at hospital discharge in patients treated with thrombolysis after myocardial infarction are common and associated with a poor outcome. Continuous left ventricular function monitoring during normal activity may provide prognostic information not available from submaximal exercise test results.

  11. Eptifibatide and Cirrhosis: Rethinking GPIIb-IIIa Inhibitors for Acute Coronary Syndrome in the Setting of Liver Dysfunction

    PubMed Central

    Weinreich, Michael; Mendoza, Dexter; Pettei, Thomas; Grayver, Evelina

    2014-01-01

    Glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, such as eptifibatide, are routinely used in the setting of acute coronary syndrome (ACS) prior to or during percutaneous coronary intervention (PCI). While numerous studies have demonstrated improved clinical outcomes with eptifibatide use, adverse effects including thrombocytopenia have also been noted. For this reason, patients with baseline thrombocytopenia or liver disease should be cautiously evaluated prior to drug administration. Here we report a case of acute profound and prolonged eptifibatide-induced thrombocytopenia in a patient with cirrhotic liver dysfunction. We propose and discuss the need for a risk stratification tool to be established for identifying which patients with ACS in the setting of chronic liver disease receive GPIIb/IIIa inhibitors. PMID:28352453

  12. Percutaneous coronary intervention for acute myocardial infarction in elderly patients with renal dysfunction: results from the Korea Acute Myocardial Infarction Registry.

    PubMed

    Lim, Sang Yup; Bae, Eun Hui; Choi, Joon Seok; Kim, Chang Seong; Ma, Seong Kwon; Ahn, Youngkeun; Jeong, Myung Ho; Kim, Weon; Woo, Jong Shin; Kim, Young Jo; Cho, Myeong Chan; Kim, Chong Jin; Kim, Soo Wan

    2013-07-01

    This study aimed to evaluate the effects of percutaneous coronary intervention (PCI) on short- and long-term major adverse cardiac events (MACE) in elderly (>75 yr old) acute myocardial infarction (AMI) patients with renal dysfunction. As part of Korea AMI Registry (KAMIR), elderly patients with AMI and renal dysfunction (GFR<60 mL/min) received either medical (n=439) or PCI (n=1,019) therapy. Primary end point was in-hospital death. Secondary end point was MACE during a 1 month and 1 yr follow-up. PCI group showed a significantly lower incidence of in-hospital death (20.0% vs 14.3%, P=0.006). Short-term and long-term MACE rates were higher in medical therapy group (31.9% vs 19.0%; 57.7% vs 31.3%, P<0.001), and this difference was mainly attributed to cardiac death (29.3% vs 17.6%; 51.9% vs 25.0%, P<0.001). MACE-free survival time after adjustment was also higher in PCI group on short-term (hazard ratio, 0.67; confidence interval, 0.45-0.98; P=0.037) and long-term follow-up (hazard ratio, 0.61, confidence interval, 0.45-0.83; P=0.002). In elderly AMI patients with renal dysfunction, PCI therapy yields favorable in-hospital and short-term and long-term MACE-free survival.

  13. Dexmedetomidine attenuates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress, mitochondrial dysfunction and apoptosis in rats

    PubMed Central

    Fu, Chunlai; Dai, Xingui; Yang, You; Lin, Mengxiang; Cai, Yeping; Cai, Shaoxi

    2016-01-01

    Previous studies have identified that dexmedetomidine (DEX) treatment can ameliorate the acute lung injury (ALI) induced by lipopolysaccharide and ischemia-reperfusion. However, the molecular mechanisms by which DEX ameliorates lung injury remain unclear. The present study investigated whether DEX, which has been reported to exert effects on oxidative stress, mitochondrial permeability transition pores and apoptosis in other disease types, can exert protective effects in lipopolysaccharide (LPS)-induced ALI by inhibiting oxidative stress, mitochondrial dysfunction and mitochondrial-dependent apoptosis. It was revealed that LPS-challenged rats exhibited significant lung injury, characterized by the deterioration of histopathology, vascular hyperpermeability, wet-to-dry weight ratio and oxygenation index (PaO2/FIO2), which was attenuated by DEX treatment. DEX treatment inhibited LPS-induced mitochondrial dysfunction, as evidenced by alleviating the cellular ATP and mitochondrial membrane potential in vitro. In addition, DEX treatment markedly prevented the LPS-induced mitochondrial-dependent apoptotic pathway in vitro (increases of cell apoptotic rate, cytosolic cytochrome c, and caspase 3 activity) and in vivo (increases of |terminal deoxynucleotidyl transferase dUTP nick-end labeling positive cells, cleaved caspase 3, Bax upregulation and Bcl-2 downregulation). Furthermore, DEX treatment markedly attenuated LPS-induced oxidative stress, as evidenced by downregulation of cellular reactive oxygen species in vitro and lipid peroxides in serum. Collectively, the present results demonstrated that DEX ameliorates LPS-induced ALI by reducing oxidative stress, mitochondrial dysfunction and mitochondrial-dependent apoptosis. PMID:27959438

  14. Dexmedetomidine attenuates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress, mitochondrial dysfunction and apoptosis in rats.

    PubMed

    Fu, Chunlai; Dai, Xingui; Yang, You; Lin, Mengxiang; Cai, Yeping; Cai, Shaoxi

    2017-01-01

    Previous studies have identified that dexmedetomidine (DEX) treatment can ameliorate the acute lung injury (ALI) induced by lipopolysaccharide and ischemia-reperfusion. However, the molecular mechanisms by which DEX ameliorates lung injury remain unclear. The present study investigated whether DEX, which has been reported to exert effects on oxidative stress, mitochondrial permeability transition pores and apoptosis in other disease types, can exert protective effects in lipopolysaccharide (LPS)‑induced ALI by inhibiting oxidative stress, mitochondrial dysfunction and mitochondrial‑dependent apoptosis. It was revealed that LPS‑challenged rats exhibited significant lung injury, characterized by the deterioration of histopathology, vascular hyperpermeability, wet‑to‑dry weight ratio and oxygenation index (PaO2/FIO2), which was attenuated by DEX treatment. DEX treatment inhibited LPS‑induced mitochondrial dysfunction, as evidenced by alleviating the cellular ATP and mitochondrial membrane potential in vitro. In addition, DEX treatment markedly prevented the LPS‑induced mitochondrial‑dependent apoptotic pathway in vitro (increases of cell apoptotic rate, cytosolic cytochrome c, and caspase 3 activity) and in vivo (increases of |terminal deoxynucleotidyl transferase dUTP nick‑end labeling positive cells, cleaved caspase 3, Bax upregulation and Bcl‑2 downregulation). Furthermore, DEX treatment markedly attenuated LPS‑induced oxidative stress, as evidenced by downregulation of cellular reactive oxygen species in vitro and lipid peroxides in serum. Collectively, the present results demonstrated that DEX ameliorates LPS‑induced ALI by reducing oxidative stress, mitochondrial dysfunction and mitochondrial-dependent apoptosis.

  15. Recurrent Acute Liver Failure Because of Acute Hepatitis Induced by Organic Solvents

    PubMed Central

    Ito, Daisuke; Tanaka, Tomohiro; Akamatsu, Nobuhisa; Ito, Kyoji; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Nakagawa, Hayato; Fujinaga, Hidetaka; Kokudo, Norihiro

    2016-01-01

    Abstract The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians

  16. Surgical Critical Care for the Patient with Sepsis and Multiple Organ Dysfunction.

    PubMed

    Kaml, Gary J; Davis, Kimberly A

    2016-12-01

    Sepsis and multiple organ dysfunction syndrome (MODS) is common in the surgical intensive care unit. Sepsis involves infection and the patient's immune response. Timely recognition of sepsis and swift application of evidence-based interventions is critical to the success of therapy. This article reviews the nature of the septic process, existing definitions of sepsis, and current evidence-based treatment strategies for sepsis and MODS. An improved understanding of the process of sepsis and its relation to MODS has resulted in clinical definitions and scoring systems that allow for the quantification of disease severity and guidelines for treatment.

  17. Acute neurotoxic effects of mancozeb and maneb in mesencephalic neuronal cultures are associated with mitochondrial dysfunction.

    PubMed

    Domico, Lisa M; Zeevalk, Gail D; Bernard, Laura P; Cooper, Keith R

    2006-09-01

    Recent studies suggest that exposure to agrochemicals may contribute to the development of idiopathic Parkinson's disease. Maneb (MB), a widely used Mn-containing ethylene-bis-dithiocarbamate (EBDC) fungicide, has been implicated in selective dopaminergic neurotoxicity. In this study, we examine the potential neurotoxicity of mancozeb (MZ), a widely used EBDC fungicide that is structurally similar to MB, but contains both Zn and Mn. Primary mesencephalic cells isolated from Sprague-Dawley embryonic day 15 rat embryos were exposed in vitro to either MZ or MB to compare their cytotoxic potential. Exposure to 10-120 microM MZ or MB for 24h resulted in a dose-dependent toxicity in both the dopamine (DA) and GABA mesencephalic populations as assessed by a functional assay for high affinity transporter activity. Consistent with this, cell viability as well as tyrosine hydroxylase-positive neurons decreased with increasing doses of MZ or MB. Toxic potencies for MZ and MB were similar and no difference in sensitivity between the DA and GABA populations was observed with the fungicides. Exposure to ethylene thiourea, the major metabolite of either MZ or MB, was not toxic, implicating the parent compound in toxicity. Both the organic and Mn metal components of the fungicides were found to contribute to toxicity. Non-toxic exposures to the fungicides decreased ATP levels in a dose-dependent manner suggesting impairment of energy metabolism. In whole mitochondrial preparations isolated from adult rat brains, MZ and MB inhibited NADH-linked state 3 respiration. Mild to moderate mitochondrial uncoupling was also observed in response to the fungicides. In conclusion, our findings indicate that acute exposure to high doses of MZ and MB produce equipotent toxic effects in both DA and GABA neurons that may be associated with perturbations in mitochondrial respiration.

  18. Irritable bowel syndrome is associated not only with organic but also psychogenic erectile dysfunction.

    PubMed

    Hsu, C-Y; Lin, C-L; Kao, C-H

    2015-01-01

    This study investigated the correlation between irritable bowel syndrome (IBS) and organic erectile dysfunction (OED) and psychogenic erectile dysfunction (PED), and analyzed the influence of various comorbidities. Data were obtained from reimbursement claims of the National Health Insurance Program in Taiwan. We selected male patients aged >20 years, who were diagnosed with IBS during the 2000-2011 period as the IBS cohort. The index date for patients with IBS was the date of their first medical visit. We excluded patients with a diagnosis of OED and PED at baseline and those without information on age and sex. The IBS to non-IBS cohorts were estimated using univariable and multivariable Cox proportional hazards regression model. Adjusted hazard ratios were determined after adjusting for age and comorbidities. The Kaplan-Meier method was used to plot the cumulative incidence of OED and PED, and a log-rank test was used to compare the cohorts. A total of 15,533 IBS patients and 62,124 controls without IBS were enrolled in our study. Among the study participants, 48.2% were 49 years of age or younger. Patients with IBS were more likely to develop erectile dysfunction (ED) than those without IBS. Patients with IBS were 2.12 times more likely to develop OED and 2.38 times more likely to develop PED than the controls. There is an increased risk of both PED and OED in patients with IBS. Not only with organic but also PED should be considered when patients with IBS complain of ED.

  19. Rehabilitation of the cavernous smooth muscle in patients with organic erectile dysfunction.

    PubMed

    Salem, H; Mostafa, T

    2012-04-01

    This study aimed at assessing the effect of regular use of intracorporeal injection (ICI), sildenafil citrate and vacuum constriction device (VCD) on cavernous smooth muscle and erectile activity. One hundred and sixty-five patients with organic erectile dysfunction were investigated for 3 months. The patient and his partner were classified prospectively after proper counselling: group I (n = 56) received ICI twice per week; group II (n = 55) received sildenafil 100 mg twice per week; and group III (n = 54) used VCD twice per week. Duplex ultrasound was carried out before and after treatment, and then, the patients were followed up for a month to assess the resumption of unaided erection. The results showed that there was significant improvement in mean peak systolic velocity (PSV) and mean cavernosal artery diameter (CAD) at the end of the treatment in all groups, being higher in the ICI group than in the other two groups. Also, the percentage of patients who resumed unaided intercourse were higher in the ICI group compared with the other two groups (17.9%, 9.1% and 3.7% respectively). It is concluded that repeated regular use of ICI, sildenafil or VCD by patients with organic erectile dysfunction has a positive impact on their cavernous blood flow and erectile activity.

  20. Trypsin is the culprit of multiple organ injury with severe acute pancreatitis.

    PubMed

    Sha, Huanchen; Ma, Qingyong; Jha, Rajiv Kumar

    2009-02-01

    The consistently high proportion of early deaths in patients with severe acute pancreatitis (SAP) has been associated mainly with the development of multiple organ dysfunction syndromes (MODS). So far, scholars believed that the main reasons of MODS with SAP are systemic microcirculation dysfunction and inflammatory mediator induced cascading effect on the basis of pancreas digesting itself. However, there is some special pathological phenomenon in the process of SAP which could not be explained by current theories. First, it has been evident that the pancreatic tissue bleeding and necrosis is special pathological change in pancreas autodigestive effect from digestive enzymes such as trypsin in SAP. However, we found that the liver, the lung, the intestine, the brain and the kidney have the same pathological changes in experimental animal models of SAP. Secondly, unlike the general inflammatory response, a significantly amount of bloody ascites and pleural effusion was often in patients with SAP and in experimental SAP animal models. It indicates that the vascular permeability significantly increased leading to the red blood cells extravasation. Thirdly, apart from dual blood supply, liver bears a strong compensatory function. However, liver has the highest incidence of injury in SAP when compared with other organs. In addition, we found a very interesting phenomenon after reading texts and clinical records. From the pancreatic venous drainage from the point of view, the farther the organ from the pancreas, the lower injury incidence rate observed. How to explain these mysteries? We postulate that the trypsin is the culprit of multiple organs dysfunction in SAP. The activated trypsin destroy the pancreas itself, causing pancreatic tissue bleeding and necrosis, at the same time, through venous flow it flow into the blood circulation and destroy the vascular endothelial barrier, leading to highly increased vascular permeability. So, a large number of bloody exudates

  1. Investigating the role of acute mental stress on endothelial dysfunction: a systematic review and meta-analysis.

    PubMed

    Xue, Yi-Tao; Tan, Qi-Wen; Li, Ping; Mou, Shan-Fang; Liu, Shu-Juan; Bao, Yue; Jiao, Hua-Chen; Su, Wen-Ge

    2015-04-01

    Chronic stress is a known risk factor for both endothelial dysfunction and cardiovascular disease (CVD), but less is known of how acute mental stress affects the vasculature. In this systematic review and meta-analysis, we analyzed the impact of acute mental stress on flow-mediated dilation (FMD), an indicator of endothelial function. We searched the Medline, Cochrane, EMBASE, and ISI Web of Knowledge databases through May 2014, to identify publications in English-language journals. The primary outcome was the change in FMD from baseline to the time of measurement. We also assessed the risk of bias and the heterogeneity of included studies. Our search identified eight prospective studies, which displayed significant heterogeneity. Four studies measured FMD while the subject was performing the task; six measured FMD after the task had been completed. The total number of participants was 164. The pooled results indicate that FMD did not change significantly while the task was being performed (pooled difference in means: -0.853; 95 % confidence interval (CI), -3.926/2.220; P = 0.586); however, FMD measured after the task was completed was significantly less than baseline (pooled difference in means: -2.450; 95 %CI, -3.925/-0.975; P = 0.001). In conclusions, our findings provide evidence that an acute stressful experience has a delayed, negative impact on the function of the endothelium. Repeated exposure to short-term stress may lead to permanent injury of the vasculature. Therefore, assessment of patients' exposure to both repeated acute mental stress and chronic stress may be useful in determining their risk of developing CVD.

  2. Phenotypic changes in colonocytes following acute stress or activation of mast cells in mice: implications for delayed epithelial barrier dysfunction

    PubMed Central

    Demaude, J; Salvador‐Cartier, C; Fioramonti, J; Ferrier, L; Bueno, L

    2006-01-01

    Background and aim Stressful life events are known to modulate the development or relapse of disease in both inflammatory bowel disease and irritable bowel disease patients but underlying mechanisms remain unclear. Stress is known to effect mast cells, interferon γ (IFN‐γ), and myosin light chain phosphorylation to trigger colonic epithelial barrier dysfunction. The aim of this study was to investigate whether acute stress induced or chemical mast cell activation impaired expression and function of epithelial tight junctions, and altered colonocyte differentiation in mice. Methods Colonic paracellular permeability was assessed as the in vivo lumen to blood ratio of 51Cr‐EDTA in different groups of mice (controls, stressed, mast cell degranulator BrX‐537A treated), pretreated or not with the mast cell stabiliser doxantrazole. Involvement of mast cells and IFN‐γ was evaluated in wild‐type and IFN‐γ deficient mice. Tight junction alteration was assessed by histology, transmission electron microscopy, and real time reverse transcription‐polymerase chain reaction. Colonocyte differentiation was determined by protein kinase C ζ (PKCζ) immunofluorescence and western blotting, and alkaline phosphatase activity assay. Results Acute stress induced a three day delayed increase in colonic paracellular permeability which involved mast cell degranulation and overproduction of IFN‐γ. The colonic epithelial barrier was morphologically altered and expression of mRNA encoding tight junction proteins ZO‐2 and occludin was decreased. Moreover, three days after acute stress, colonocyte differentiation was reduced, as shown by decreased expression of both PKCζ isotype and alkaline phosphatase. Conclusion These data highlight new mechanisms whereby an acute stress acts on the gastrointestinal tract by inducing alterations in colonocyte differentiation and decreased expression of mRNA encoding tight junction proteins. Thus phenotypic changes in colonocytes could

  3. Percutaneous Coronary Intervention for Acute Myocardial Infarction in Elderly Patients with Renal Dysfunction: Results from the Korea Acute Myocardial Infarction Registry

    PubMed Central

    Lim, Sang Yup; Bae, Eun Hui; Choi, Joon Seok; Kim, Chang Seong; Ma, Seong Kwon; Ahn, Youngkeun; Jeong, Myung Ho; Kim, Weon; Woo, Jong Shin; Kim, Young Jo; Cho, Myeong Chan; Kim, Chong Jin

    2013-01-01

    This study aimed to evaluate the effects of percutaneous coronary intervention (PCI) on short- and long-term major adverse cardiac events (MACE) in elderly (>75 yr old) acute myocardial infarction (AMI) patients with renal dysfunction. As part of Korea AMI Registry (KAMIR), elderly patients with AMI and renal dysfunction (GFR<60 mL/min) received either medical (n=439) or PCI (n=1,019) therapy. Primary end point was in-hospital death. Secondary end point was MACE during a 1 month and 1 yr follow-up. PCI group showed a significantly lower incidence of in-hospital death (20.0% vs 14.3%, P=0.006). Short-term and long-term MACE rates were higher in medical therapy group (31.9% vs 19.0%; 57.7% vs 31.3%, P<0.001), and this difference was mainly attributed to cardiac death (29.3% vs 17.6%; 51.9% vs 25.0%, P<0.001). MACE-free survival time after adjustment was also higher in PCI group on short-term (hazard ratio, 0.67; confidence interval, 0.45-0.98; P=0.037) and long-term follow-up (hazard ratio, 0.61, confidence interval, 0.45-0.83; P=0.002). In elderly AMI patients with renal dysfunction, PCI therapy yields favorable in-hospital and short-term and long-term MACE-free survival. PMID:23853485

  4. Assessment of heat shock proteins and endothelial dysfunction in acute pulmonary embolism.

    PubMed

    İn, Erdal; Deveci, Figen; Kaman, Dilara

    2016-06-01

    We determined the levels of some heat shock proteins (HSP27, HSP70, and HSP90), L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) levels in patients with acute pulmonary embolism. The present case-control study comprised a healthy control group (n = 57) and patients with acute pulmonary embolism (n = 84). HSPs, L-arginine, ADMA, and SDMA levels were measured in all of the cases. The mean age of the control group was 56.72 ± 8.44 years, and the mean age of the patients with acute pulmonary embolism was 60.20 ± 16.56 years (P = 0.104). Compared with controls, patients with acute pulmonary embolism had significantly higher mean serum HSP27, HSP90, and ADMA levels, whereas the mean serum L-arginine and SDMA levels were lower (P < 0.001, for all parameters). In patients with acute pulmonary embolism serum HSP27, HSP70, and ADMA levels were negatively correlated with partial pressures of arterial oxygen levels (r = -0.281, P = 0.01; r = -0.263, P = 0.016; and r = -0.275, P = 0.011, respectively) and arterial oxygen saturation (r = -0.225, P = 0.039; r = -0.400, P < 0.001; r = -0.299, P = 0.006, respectively). The findings of the present study demonstrated that oxidative stress and endothelial damage increase in acute pulmonary embolism.

  5. Phase 1 Study of Pazopanib in Patients with Advanced Solid Tumors and Hepatic Dysfunction: A National Cancer Institute Organ Dysfunction Working Group Study

    PubMed Central

    Shibata, Stephen I; Chung, Vincent; Synold, Timothy; Longmate, Jeffrey; Suttle, A Benjamin; Ottesen, Lone H; Lenz, Heinz-Josef; Kummar, Shivaani; Harvey, R Donald; Hamilton, Anne; O’Neil, Bert; Sarantopoulos, John; LoRusso, Patricia; Rudek, Michelle A; Dowlati, Afshin; Mulkerin, Daniel; Belani, Chandra P.; Gandhi, Leena; Lau, Cecilia; Ivy, S. Percy; Newman, Edward M.

    2013-01-01

    Purpose Pazopanib is a potent, multi-targeted receptor tyrosine kinase inhibitor; however, there is limited information regarding the effects of liver function on pazopanib metabolism and pharmacokinetics (PK). The objective of this study was to establish the maximum tolerated dose (MTD) and PK profile of pazopanib in patients with varying degrees of hepatic dysfunction. Experimental Design Patients with any solid tumors or lymphoma were stratified into four groups based on the degree of hepatic dysfunction according to the National Cancer Institute Organ Dysfunction Working Group (NCI ODWG) criteria. Pazopanib was given orally once a day on a 21-day cycle. A modified 3+3 design was used. Results Ninety eight patients were enrolled. Patients in the mild group tolerated 800 mg per day. The moderate and severe groups tolerated 200 mg per day. Pharmacokinetic data in the mild group were similar to the data in the normal group. Comparison of the median Cmax and AUC(0–24) in the moderate or severe groups at 200 mg per day to the values in the normal and mild groups at 800 mg per day indicated less than dose-proportional systemic exposures in patients with moderate and severe hepatic impairment. This suggests that the lower MTD in the moderate and severe group is not due to a decrease in drug clearance or alteration in the proportion of metabolites. Conclusions In patients with mild liver dysfunction, pazopanib is well tolerated at the FDA-approved dose of 800 mg per day. Patients with moderate and severe liver dysfunction tolerated 200 mg per day. PMID:23653147

  6. Berberine attenuates adverse left ventricular remodeling and cardiac dysfunction after acute myocardial infarction in rats: role of autophagy.

    PubMed

    Zhang, Yao-Jun; Yang, Shao-Hua; Li, Ming-Hui; Iqbal, Javaid; Bourantas, Christos V; Mi, Qiong-Yu; Yu, Yi-Hui; Li, Jing-Jing; Zhao, Shu-Li; Tian, Nai-Liang; Chen, Shao-Liang

    2014-12-01

    The present study aimed to test the hypothesis that berberine, a plant-derived anti-oxidant, attenuates adverse left ventricular remodelling and improves cardiac function in a rat model of myocardial infarction (MI). Furthermore, the potential mechanisms that mediated the cardioprotective actions of berberine, in particular the effect on autophagy, were also investigated. Acute MI was induced by ligating the left anterior descending coronary artery of Sprague-Dawley rats. Cardiac function was assessed by transthoracic echocardiography. The protein activity/levels of autophagy related to signalling pathways (e.g. LC-3B, Beclin-1) were measured in myocardial tissue by immunohistochemical staining and western blot. Four weeks after MI, berberine significantly prevented cardiac dysfunction and adverse cardiac remodelling. MI rats treated with low dose berberine (10 mg/kg per day) showed higher left ventricular ejection fraction and fractional shortening than those treated with high-dose berberine (50 mg/kg per day). Both doses reduced interstitial fibrosis and post-MI adverse cardiac remodelling. The cardioprotective action of berberine was associated with increased LC-3B II and Beclin-1 expressions. Furthermore, cardioprotection with berberine was potentially related to p38 MAPK inhibition and phospho-Akt activation. The present in vivo study showed that berberine is effective in promoting autophagy, and subsequently attenuating left ventricular remodelling and cardiac dysfunction after MI. The potential underlying mechanism is augmentation of autophagy through inhibition of p38 MAPK and activation of phospho-Akt signalling pathways.

  7. A study of acute muscle dysfunction with particular reference to dengue myopathy

    PubMed Central

    Verma, Rajesh; Holla, Vikram V.; Kumar, Vijay; Jain, Amita; Husain, Nuzhat; Malhotra, Kiran Preet; Garg, Ravindra Kumar; Malhotra, Hardeep Singh; Sharma, Praveen Kumar; Kumar, Neeraj

    2017-01-01

    Background: Acute myopathy is a common cause of acute motor quadriparesis which has various etiologies with different courses of illness and prognosis depending on the cause. Understanding this diversity helps us in proper approach toward diagnosis, predicting the prognosis, and possible complications and in improving the treatments that are being provided. This study was planned to study the clinical, electrophysiological, and etiological profile of patients presenting with acute myopathy. We also studied how dengue-related acute myopathy differs from other causes and also difference between myopathy due to myositis and hypokalemia in cases of dengue. Materials and Methods: This was a prospective, observational study involving all clinically suspected cases of acute myopathy of not more than 4 weeks duration with raised serum creatine kinase (CK) level. They were subjected to detailed clinical evaluation along with hematological, biochemical, microbiological, and electrophysiological studies and followed-up for outcome at 1 and 3 months. Muscle biopsy and histopathological examination were done in selected patients after taking informed consent. Statistical analysis was performed by appropriate methods using SPSS version 16.0 (Chicago, IL, USA). Results: We evaluated thirty patients of acute myopathy with raised CK level. Seventeen patients had fever, 11 had myalgia, and 5 had skin lesions. All presented with symmetric weakness, 17 (56.7%) patients having predominantly proximal weakness, neck or truncal weakness in 6 (20%), hyporeflexia in 12 (40%), with mean Medical Research Council (MRC) sum score of 46.67 ± 6.0. Eight (mean modified Barthel index [MBI] at presentation - 15 ± 3.7) patients had poor functional status according to MBI and 15 according to modified Rankin scale (MRS) (mean MRS score - 2.5 ± 1.2). Etiology was dengue viral infection in 14 patients; hypokalemia due to various causes other than dengue in 8; pyomyositis in 3; dermatomyositis

  8. 17-DMAG, an HSP90 Inhibitor, Ameliorates Multiple Organ Dysfunction Syndrome via Induction of HSP70 in Endotoxemic Rats

    PubMed Central

    Wang, Yi-Li; Shen, Hsin-Hsueh; Cheng, Pao-Yun; Chu, Yen-Ju; Hwang, Hwong-Ru; Lam, Kwok-Keung; Lee, Yen-Mei

    2016-01-01

    Sepsis is a systemic inflammatory disorder, accompanied with elevated oxidative stress, leading to multiple organ dysfunction syndrome (MODS), and disseminated intravascular coagulation. 17-Dimethylaminoethylamino- 17-demethoxygeldanamycin (17-DMAG), a heat shock protein (HSP) 90 inhibitor, has been reported to possess anti-inflammatory effects. In this study, the beneficial effects of 17-DMAG on lipopolysaccharide (LPS) induced MODS and DIC was evaluated in anesthetized rats. 17-DMAG (5 mg/kg, i.p.) was significantly increased survival rate, and prevented hypotension in LPS (30 mg/kg i.v. infused for 4 h) induced endotoxemia. The elevated levels of alanine aminotransferase (ALT), creatine phosphokinase (CPK), lactate dehydrogenase, creatinine, nitric oxide (NO) metabolites, IL-6, and TNF-α in LPS-exposed rat plasma were significantly reduced by 17-DMAG. Moreover, 17-DMAG suppressed LPS-induced superoxide anion production and caspase 3 activation in heart tissues. LPS induced the prolongation of prothrombin time, and a pronounced decrease in platelet count, which were improved by 17-DMAG. 17-DMAG markedly induced HSP70 and heme oxygenase (HO)-1, and suppressed inducible nitric oxide synthase (iNOS) and phosphorylated NF-κB p65 protein expression in organs 6 h after LPS initiation. Pretreatment with high dose of quercetin (300 mg/kg, i.p.), as an HSP70 inhibitor, reversed the beneficial effects of 17-DMAG on survival rate, plasma levels of ALT, CPK, creatinine, IL-6, and NO metabolites, iNOS induction, and caspase-3 activation in LPS-treated rats. In conclusion, 17-DMAG possesses the anti-inflammatory and antioxidant effects that were proved through LPS-induced acute inflammation, which is associated with induction of HSP70 and HO-1, leading to prevent MODS in sepsis. PMID:27224288

  9. Anti-inflammatory treatment in dysfunction of pulmonary surfactant in meconium-induced acute lung injury.

    PubMed

    Mokra, D; Drgova, A; Kopincova, J; Pullmann, R; Calkovska, A

    2013-01-01

    Inflammation, oxidation, lung edema, and other factors participate in surfactant dysfunction in meconium aspiration syndrome (MAS). Therefore, we hypothesized that anti-inflammatory treatment may reverse surfactant dysfunction in the MAS model. Oxygen-ventilated rabbits were given meconium intratracheally (25 mg/ml, 4 ml/kg; Mec) or saline (Sal). Thirty minutes later, meconium-instilled animals were treated by glucocorticoids budesonide (0.25 mg/kg, i.t.) and dexamethasone (0.5 mg/kg, i.v.), or phosphodiesterase inhibitors aminophylline (2 mg/kg, i.v.) and olprinone (0.2 mg/kg, i.v.), or the antioxidant N-acetylcysteine (10 mg/kg, i.v.). Healthy, non-ventilated animals served as controls (Con). At the end of experiments, left lung was lavaged and a differential leukocyte count in sediment was estimated. The supernatant of lavage fluid was adjusted to a concentration of 0.5 mg phospholipids/ml. Surfactant quality was evaluated by capillary surfactometer and expressed by initial pressure and the time of capillary patency. The right lung was used to determine lung edema by wet/dry (W/D) weight ratio. Total antioxidant status (TAS) in blood plasma was evaluated. W/D ratio increased and capillary patency time shortened significantly, whereas the initial pressure increased and TAS decreased insignificantly in Sal vs. Con groups. Meconium instillation potentiated edema formation and neutrophil influx into the lungs, reduced capillary patency and TAS, and decreased the surfactant quality compared with both Sal and Con groups (p > 0.05). Each of the anti-inflammatory agents reduced lung edema and neutrophil influx into the lung and partly reversed surfactant dysfunction in the MAS model, with a superior effect observed after glucocorticoids and the antioxidant N-acetylcysteine.

  10. The relationship between gut-derived bacteria and the development of the multiple organ dysfunction syndrome.

    PubMed Central

    Nieuwenhuijzen, G A; Deitch, E A; Goris, R J

    1996-01-01

    Abnormal colonisation, infections of gut origin and bacterial translocation are all signs of gut failure that have been hypothesised as being implicated in the pathogenesis of the multiple organ dysfunction syndrome (MODS). We have summarised published experimental and clinical studies that have tried to correlate the occurrence or prevention of these phenomena with the development of MODS. We conclude that in some patients loss of intestinal barrier function or the onset of infection precedes the development of MODS. In other patients, however, this relationship is not so clear and it seems that these are epiphenoma of critical illness and may reflect a failure of the host's immune and mechanical defence systems. The causal relationship between these phenomena and the development of MODS is complex and needs further clarification. PMID:8982828

  11. Long term prognosis of acute coronary syndrome with chronic renal dysfunction treated in different therapy units at department of cardiology: a retrospective cohort study.

    PubMed

    Fu, Cong; Sheng, Zulong; Yao, Yuyu; Wang, Xin; Yu, Chaojun; Ma, Genshan

    2015-01-01

    Coronary care unit is common in hospitals and clinical centers which offer intensive care and therapy for severe coronary artery disease patients. However, if coronary care unit could improve the long term prognosis of acute coronary syndrome patients with renal dysfunction remain unknown. Accordingly, we designed this study to evaluate the differences of incidence of major adverse cardiovascular events for acute coronary syndromes patients with renal dysfunction who treated in coronary care unit or normal unit. The primary end point was all cause mortality. A total of 414 acute coronary syndromes patients with renal dysfunction involved in the study. The results showed that during 12-48 months follow-up, death of any cause occurred in 1.8% patients (4 of 247) in coronary care unit group, as compared with 1.8% in the normal group (3 of 167) (hazard ratio, 1.098; 95% confidence interval, 0.246 to 4.904; P=0.903). Kaplan-Meier survival analysis showed that there were no significant differences between the two groups with respect to the risk of death (P=0.903), revascularization (P=0.948), stroke (P=0.542), heart failure (P=0.198). This trial firstly revealed that acute coronary syndromes patients with renal dysfunction treated in coronary care unit and normal units. Our study showed that acute coronary syndromes patients with renal dysfunction treated in coronary care unit obtained no significant benefits compared with patients in normal units, although there was a declining tendency of the risk of major adverse cardiovascular effectswith patients in coronary care unit.

  12. Long term prognosis of acute coronary syndrome with chronic renal dysfunction treated in different therapy units at department of cardiology: a retrospective cohort study

    PubMed Central

    Fu, Cong; Sheng, Zulong; Yao, Yuyu; Wang, Xin; Yu, Chaojun; Ma, Genshan

    2015-01-01

    Coronary care unit is common in hospitals and clinical centers which offer intensive care and therapy for severe coronary artery disease patients. However, if coronary care unit could improve the long term prognosis of acute coronary syndrome patients with renal dysfunction remain unknown. Accordingly, we designed this study to evaluate the differences of incidence of major adverse cardiovascular events for acute coronary syndromes patients with renal dysfunction who treated in coronary care unit or normal unit. The primary end point was all cause mortality. A total of 414 acute coronary syndromes patients with renal dysfunction involved in the study. The results showed that during 12-48 months follow-up, death of any cause occurred in 1.8% patients (4 of 247) in coronary care unit group, as compared with 1.8% in the normal group (3 of 167) (hazard ratio, 1.098; 95% confidence interval, 0.246 to 4.904; P=0.903). Kaplan-Meier survival analysis showed that there were no significant differences between the two groups with respect to the risk of death (P=0.903), revascularization (P=0.948), stroke (P=0.542), heart failure (P=0.198). This trial firstly revealed that acute coronary syndromes patients with renal dysfunction treated in coronary care unit and normal units. Our study showed that acute coronary syndromes patients with renal dysfunction treated in coronary care unit obtained no significant benefits compared with patients in normal units, although there was a declining tendency of the risk of major adverse cardiovascular effectswith patients in coronary care unit. PMID:26770436

  13. Serum concentrations of vitamin D and organ dysfunction in patients with severe sepsis and septic shock

    PubMed Central

    Alves, Fernanda Sampaio; Freitas, Flavio Geraldo Resende; Bafi, Antonio Tonete; Azevedo, Luciano Cesar Pontes; Machado, Flavia Ribeiro

    2015-01-01

    Objectives To evaluate the serum concentrations of vitamin D and their variations in patients with severe sepsis or septic shock and in control subjects upon admission and after 7 days of hospitalization in the intensive care unit and to correlate these concentrations with the severity of organ dysfunction. Methods This case-control, prospective, observational study involved patients aged > 18 years with severe sepsis or septic shock paired with a control group. Serum vitamin D concentrations were measured at inclusion (D0) and on the seventh day after inclusion (D7). Severe deficiency was defined as vitamin D levels < 10ng/ml, deficiency as levels between 10 and 20ng/ml, insufficiency as levels between 20 and 30ng/ml, and sufficiency as levels ≥ 30ng/mL. We considered a change to a higher ranking, together with a 50% increase in the absolute concentration, to represent an improvement. Results We included 51 patients (26 with septic shock and 25 controls). The prevalence of vitamin D concentration ≤ 30ng/ml was 98%. There was no correlation between the serum concentration of vitamin D at D0 and the SOFA score at D0 or D7 either in the general population or in the group with septic shock. Patients with improvement in vitamin D deficiency had an improved SOFA score at D7 (p = 0.013). Conclusion In the population studied, patients with septic shock showed improvement in the serum concentrations of vitamin D on the seventh day compared with the controls. We also found a correlation between higher vitamin D concentrations and a greater decrease in the severity of organ dysfunction. PMID:26761476

  14. Cardiorenal Syndrome Type 1: Renal Dysfunction in Acute Decompensated Heart Failure

    PubMed Central

    Prins, Kurt W.; Thenappan, Thenappan; Markowitz, Jeremy S.; Pritzker, Marc R.

    2016-01-01

    Objective To present a review of cardiorenal syndrome type 1 (CRS1). Methods Review of the literature. Results Acute kidney injury occurs in approximately one-third of patients with acute decompensated heart failure (ADHF) and the resultant condition was named CRS1. A growing body of literature shows CRS1 patients are at high risk for poor outcomes, and thus there is an urgent need to understand the pathophysiology and subsequently develop effective treatments. In this review we discuss prevalence, proposed pathophysiology including hemodynamic and nonhemodynamic factors, prognosticating variables, data for different treatment strategies, and ongoing clinical trials and highlight questions and problems physicians will face moving forward with this common and challenging condition. Conclusion Further research is needed to understand the pathophysiology of this complex clinical entity and to develop effective treatments. PMID:27158218

  15. Evaluation of an Acute RNAi-Mediated Therapeutic for Visual Dysfunction Associated with Traumatic Brain Injury

    DTIC Science & Technology

    2013-10-01

    water from the brain to the blood and significantly impacts on brain swelling. We also show cognitive improvement in mice with focal cerebral...brain injury ( TBI ) is the leading cause of death in children and young adults globally. Malignant cerebral edema plays a major role in the...pathophysiology which evolves after severe TBI . Added to this is the significant morbidity and mortality from cerebral edema associated with acute stroke

  16. Cognitive Dysfunction and Malnutrition Are Independent Predictor of Dysphagia in Patients with Acute Exacerbation of Congestive Heart Failure

    PubMed Central

    Yamanaka, Shinsuke; Takahashi, Yoshimi; Fujita, Hiroshi; Yamaguchi, Nobuhiro; Onoue, Noriko; Ishizuka, Takeshi; Shinozaki, Tsuyoshi; Kohzuki, Masahiro

    2016-01-01

    Early detection and intervention for dysphagia is important in patients with congestive heart failure (CHF). However, previous studies have focused on how many patients with dysphagia develop CHF. Studies focusing on the comorbidity of dysphagia in patients with CHF are rare. Additionally, risk factors for dysphagia in patients with CHF are unclear. Thus, the aim of this study was to clarify risk factors for dysphagia in patients with acute exacerbation of CHF. A total of 105 patients, who were admitted with acute exacerbation of CHF, were enrolled. Clinical interviews, blood chemistry analysis, electrocardiography, echocardiography, Mini-Mental State Examination (MMSE), exercise tolerance tests, phonatory function tests, and evaluation of activities of daily living (ADL) and nutrition were conducted on admission. After attending physicians permitted the drinking of water, swallowing screening tests were performed. Patients were divided into a dysphagia group (DG) or a non-dysphagia group (non-DG) based on Functional Oral Intake Scale level. Among the 105 patients, 38 had dysphagia. A greater number of patients had history of aspiration pneumonia and dementia, and there was a higher age, N-terminal pro-B-type natriuretic peptide level in the DG compared with the non-DG. MMSE scores, exercise tolerance, phonatory function, status of ADL, nutrition, albumin, and transthyretin were lower in the DG compared with the non-DG. In multivariate analysis, after adjusting for age and sex, MMSE, BI score, and transthyretin was independently associated with dysphagia. Comorbidity of dysphagia was 36.1% in patients with acute exacerbation of CHF, and cognitive dysfunction and malnutrition may be an independent predictor of dysphagia. PMID:27898735

  17. Catheter-Directed Therapy in Acute Pulmonary Embolism with Right Ventricular Dysfunction: A Promising Modality to Provide Early Hemodynamic Recovery

    PubMed Central

    Dilektasli, Asli Gorek; Cetinoglu, Ezgi Demirdogen; Acet, Nilufer Aylin; Erdogan, Cuneyt; Ursavas, Ahmet; Ozkaya, Guven; Coskun, Funda; Karadag, Mehmet; Ege, Ercument

    2016-01-01

    Background Catheter-directed therapy (CDT) for pulmonary embolism (PE) is considered as an alternative to systemic thrombolysis (ST) in patients with hemodynamically unstable acute PE who are considered at high bleeding risk for ST. We aimed to evaluate the efficacy and safety of CDT in the management of acute PE with right ventricular dysfunction (RVD). The primary outcomes were mortality, clinical success, and complications. Secondary outcomes were change in hemodynamic parameters in the first 24 hours following the procedure. Material/Methods Medical records of consecutive patients diagnosed as having acute massive or submassive PE with accompanying RVD treated by immediate CDT at our institution from January 2007 to January 2014 were reviewed. Patient characteristics, mortality, achievement of clinical success, and minor and major bleeding complications were analyzed in the overall study group, as well as massive vs. submassive PE subgroups. Change in hemodynamic parameters in the second, eighth, and 24th hours after the CDT procedure were also analyzed. Results The study included 15 consecutive patients (M/F=10/5) with a mean age of 54.2±16.6 years who underwent immediate CDT. Nine of the patients had submassive PE, and 6 had massive PE. In-hospital mortality rate was 13.3% (95% CI, 0.04–0.38). One major, but not life-threatening, bleeding episode was evident in the whole group. Hemodynamic parameters were stabilized and clinical success was achieved in 14/15 (93.3%; 95% CI, 70.2–98.8) of the patients in the first 24 hours. Notably, the hemodynamic recovery was significantly evident in the first 8 hours after the procedure. Conclusions CDT is a promising treatment option for patients with acute PE with RVD with no fatal bleeding complication. In experienced centers, CDT should be considered as a first-line treatment for patients with acute PE and RVD and contraindications for ST, with the advantage of providing early hemodynamic recovery. PMID:27081754

  18. Acute cardiogenic pulmonary oedema with multiorgan dysfunction--still to learn more about nitrobenzene poisoning.

    PubMed

    Agrawal, Avinash; Gutch, Manish; Arora, Rahul; Jain, Nirdesh

    2011-12-20

    Nitrobenzene is a nitrite compound often used in polishes or solvents. Its toxic effects are due to its ability to induce methaemoglobinaemia. The clinical presentation of this poisoning varies according to the concentration of methaemoglobin level in blood. The importance of early identification of the compound on the basis of clinical suspicion corroborative with methaemoglobin level with timely intervention is required to prevent fatal outcome. It is also important to take care of the secondary cycling of nitrobenzene from body stores to prevent secondary recurrence of symptoms in patients after heavy exposure. Here author reports a rare case of accidental poisoning with nitrobenzene presented with respiratory distress and cyanosis. On investigation, he was diagnosed to have cardiogenic pulmonary oedema and multiorgan dysfunction. The urgent institution of methylene blue as specific antidote along with haemodynamic and ventilatory support was proved crucial for life saving of the patient.

  19. Acute cardiogenic pulmonary oedema with multiorgan dysfunction – still to learn more about nitrobenzene poisoning

    PubMed Central

    Agrawal, Avinash; Gutch, Manish; Arora, Rahul; Jain, Nirdesh

    2011-01-01

    Nitrobenzene is a nitrite compound often used in polishes or solvents. Its toxic effects are due to its ability to induce methaemoglobinaemia. The clinical presentation of this poisoning varies according to the concentration of methaemoglobin level in blood. The importance of early identification of the compound on the basis of clinical suspicion corroborative with methaemoglobin level with timely intervention is required to prevent fatal outcome. It is also important to take care of the secondary cycling of nitrobenzene from body stores to prevent secondary recurrence of symptoms in patients after heavy exposure. Here author reports a rare case of accidental poisoning with nitrobenzene presented with respiratory distress and cyanosis. On investigation, he was diagnosed to have cardiogenic pulmonary oedema and multiorgan dysfunction. The urgent institution of methylene blue as specific antidote along with haemodynamic and ventilatory support was proved crucial for life saving of the patient. PMID:22669995

  20. Kynurenine–3–monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis

    PubMed Central

    Mole, Damian J; Webster, Scott P; Uings, Iain; Zheng, Xiaozhong; Binnie, Margaret; Wilson, Kris; Hutchinson, Jonathan P; Mirguet, Olivier; Walker, Ann; Beaufils, Benjamin; Ancellin, Nicolas; Trottet, Lionel; Bénéton, Véronique; Mowat, Christopher G; Wilkinson, Martin; Rowland, Paul; Haslam, Carl; McBride, Andrew; Homer, Natalie ZM; Baily, James E; Sharp, Matthew GF; Garden, O James; Hughes, Jeremy; Howie, Sarah EM; Holmes, Duncan S; Liddle, John; Iredale, John P

    2015-01-01

    Acute pancreatitis (AP) is a common and devastating inflammatory condition of the pancreas that is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death1,2 Acute mortality from AP-MODS exceeds 20%3 and for those who survive the initial episode, their lifespan is typically shorter than the general population4. There are no specific therapies available that protect individuals against AP-MODS. Here, we show that kynurenine-3-monooxygenase (KMO), a key enzyme of tryptophan metabolism5, is central to the pathogenesis of AP-MODS. We created a mouse strain deficient for Kmo with a robust biochemical phenotype that protected against extrapancreatic tissue injury to lung, kidney and liver in experimental AP-MODS. A medicinal chemistry strategy based on modifications of the kynurenine substrate led to the discovery of GSK180 as a potent and specific inhibitor of KMO. The binding mode of the inhibitor in the active site was confirmed by X-ray co-crystallography at 3.2 Å resolution. Treatment with GSK180 resulted in rapid changes in levels of kynurenine pathway metabolites in vivo and afforded therapeutic protection against AP-MODS in a rat model of AP. Our findings establish KMO inhibition as a novel therapeutic strategy in the treatment of AP-MODS and open up a new area for drug discovery in critical illness. PMID:26752518

  1. Exposure to volatile organic compounds and kidney dysfunction in thin film transistor liquid crystal display (TFT-LCD) workers.

    PubMed

    Chang, Ta-Yuan; Huang, Kuei-Hung; Liu, Chiu-Shong; Shie, Ruei-Hao; Chao, Keh-Ping; Hsu, Wen-Hsin; Bao, Bo-Ying

    2010-06-15

    Many volatile organic compounds (VOCs) are emitted during the manufacturing of thin film transistor liquid crystal displays (TFT-LCDs), exposure to some of which has been reported to be associated with kidney dysfunction, but whether such an effect exists in TFT-LCD industry workers is unknown. This cross-sectional study aimed to investigate the association between exposure to VOCs and kidney dysfunction among TFT-LCD workers. The results showed that ethanol (1811.0+/-1740.4 ppb), acetone (669.0+/-561.0 ppb), isopropyl alcohol (187.0+/-205.3 ppb) and propylene glycol monomethyl ether acetate (PGMEA) (102.9+/-102.0 ppb) were the four dominant VOCs present in the workplace. The 63 array workers studied had a risk of kidney dysfunction 3.21-fold and 3.84-fold that of 61 cell workers and 18 module workers, respectively. Workers cumulatively exposed to a total level of isopropyl alcohol, PGMEA and propylene glycol monomethyl ether> or =324 ppb-year had a significantly higher risk of kidney dysfunction (adjusted OR=3.41, 95% CI=1.14-10.17) compared with those exposed to <25 ppb-year after adjustment for potential confounding factors. These findings indicated that array workers might be the group at greatest risk of kidney dysfunction within the TFT-LCD industry, and cumulative exposure to specific VOCs might be associated with kidney dysfunction.

  2. Nonlinear Analysis of Sensory Organization Test for Subjects with Unilateral Vestibular Dysfunction

    PubMed Central

    Lin, Chen; Chang, Fu-Ling; Lo, Men-Tzung

    2014-01-01

    Vestibular disorder is the cause of approximately 50% of dizziness in older people. The vestibular system is a critical postural control mechanism, and posturography analysis is helpful for diagnosing vestibular disorder. In clinical practice, the sensory organization test (SOT) is used to quantify postural control in an upright stance under different test conditions. However, both aging and vestibular disorder cause declines of postural control mechanisms. The aim of this study was to enhance the performance of the SOT using a nonlinear algorithm of empirical mode decomposition (EMD) and to verify the differences of effects caused by aging and/or illnesses benefits to clinical diagnosis. A total of 51 subjects belonging to 3 groups—healthy-young, healthy-elderly and dizzy—were recruited for this study. New dynamic parameters of the SOT were derived from the center of pressure (COP) signals. EMD served as an adaptive filter bank to derive the low- and high-frequency components of the COP. The effects on four ratios of sensory analysis caused by aging and vestibular disorder can be investigated for the specific frequency bands. According to our findings, new SOT parameters derived from the component with the specific frequency band more sensitively reflect the functional condition of vestibular dysfunction. Furthermore, both aging and vestibular dysfunction caused an increase in magnitude for the low-frequency component of the AP-direction COP time series. In summary, the low-frequency fluctuation reflects the stability of postural control, while the high-frequency fluctuation is sensitive to the functional condition of the sensory system. EMD successfully improved the accuracy of SOT measurements in this investigation. PMID:24632582

  3. Nonlinear analysis of sensory organization test for subjects with unilateral vestibular dysfunction.

    PubMed

    Yeh, Jia-Rong; Hsu, Li-Chi; Lin, Chen; Chang, Fu-Ling; Lo, Men-Tzung

    2014-01-01

    Vestibular disorder is the cause of approximately 50% of dizziness in older people. The vestibular system is a critical postural control mechanism, and posturography analysis is helpful for diagnosing vestibular disorder. In clinical practice, the sensory organization test (SOT) is used to quantify postural control in an upright stance under different test conditions. However, both aging and vestibular disorder cause declines of postural control mechanisms. The aim of this study was to enhance the performance of the SOT using a nonlinear algorithm of empirical mode decomposition (EMD) and to verify the differences of effects caused by aging and/or illnesses benefits to clinical diagnosis. A total of 51 subjects belonging to 3 groups--healthy-young, healthy-elderly and dizzy--were recruited for this study. New dynamic parameters of the SOT were derived from the center of pressure (COP) signals. EMD served as an adaptive filter bank to derive the low- and high-frequency components of the COP. The effects on four ratios of sensory analysis caused by aging and vestibular disorder can be investigated for the specific frequency bands. According to our findings, new SOT parameters derived from the component with the specific frequency band more sensitively reflect the functional condition of vestibular dysfunction. Furthermore, both aging and vestibular dysfunction caused an increase in magnitude for the low-frequency component of the AP-direction COP time series. In summary, the low-frequency fluctuation reflects the stability of postural control, while the high-frequency fluctuation is sensitive to the functional condition of the sensory system. EMD successfully improved the accuracy of SOT measurements in this investigation.

  4. A Nationwide Population-Based Cohort Study of Migraine and Organic-Psychogenic Erectile Dysfunction

    PubMed Central

    Wu, Szu-Hsien; Chuang, Eric; Chuang, Tien-Yow; Lin, Cheng-Li; Lin, Ming-Chia; Yen, Der-Jen; Kao, Chia-Hung

    2016-01-01

    Abstract As chronic illnesses and chronic pain are related to erectile dysfunction (ED), migraine as a prevalent chronic disorder affecting lots of people all over the world may negatively affect quality of life as well as sexual function. However, a large-scale population-based study of erectile dysfunction and other different comorbidities in patients with migraine is quite limited. This cohort longitudinal study aimed to estimate the association between migraine and ED using a nationwide population-based database in Taiwan. The data used for this cohort study were retrieved from the Longitudinal Health Insurance Database 2000 in Taiwan. We identified 5015 patients with migraine and frequency matched 20,060 controls without migraine from 2000 to 2011. The occurrence of ED was followed up until the end of 2011. We used Cox proportional hazard regression models to analyze the risks of ED. The overall incidence of ED was 1.78-fold greater in the migraine cohort than in the comparison cohort (23.3 vs 10.5 per 10,000 person-years; 95% confidence interval [CI] = 1.31–2.41). Furthermore, patients with migraine were 1.75-fold more likely to develop organic ED (95% CI = 1.27–2.41) than were the comparison cohort. The migraine patients with anxiety had a 3.6-fold higher HR of having been diagnosed with ED than the comparison cohort without anxiety (95% CI, 2.10–6.18). The results support that patients with migraine have a higher incidence of being diagnosed with ED, particularly in the patient with the comorbidity of anxiety. PMID:26962838

  5. Corticosteroids prevent acute lung dysfunction caused by thoracic irradiation in unanesthetized sheep

    SciTech Connect

    Loyd, J.E.; Bolds, J.M.; Wickersham, N.; Malcolm, A.W.; Brigham, K.L.

    1988-11-01

    We sought to determine the effect of corticosteroid therapy in a new acute model of oxidant lung injury, thoracic irradiation in awake sheep. Sheep were irradiated with 1,500 rads to the whole chest except for blocking the heart and adjacent ventral lung. Seven experimental sheep were given methylprednisolone (1 g intravenously every 6 h for four doses) and thoracic irradiation; control sheep received only irradiation. In irradiated control sheep, lung lymph flow increased from baseline (7.6 ml/h) to peak at 3 h (13.2), and lung lymph protein clearance increased from 5.1 to 9.7 ml/h. Mean pulmonary artery pressure increased in the irradiated control sheep from 19 to 32.4 cm H/sub 2/O, whereas the lung lymph thromboxane concentration increased from 0.09 to 6.51 ng/ml at 3 h. Arterial oxygen tension in irradiated control sheep fell gradually from 86 mm Hg at baseline to 65 mm Hg at 8 h. Methylprednisolone administration significantly prevented the increase in lung lymph protein clearance, mean pulmonary artery pressure, and lung lymph thromboxane concentration. Methylprednisolone also prevented the fall in arterial oxygen tension after thoracic irradiation, but did not prevent a further decrease in lymphocytes in blood or lung lymph after radiation. We conclude that corticosteroid therapy prevents most of the acute physiologic changes caused by thoracic irradiation in awake sheep.

  6. Miglitol improves postprandial endothelial dysfunction in patients with acute coronary syndrome and new-onset postprandial hyperglycemia

    PubMed Central

    2013-01-01

    Background Hyperglycemia, a risk factor for development of cardiovascular disease, causes endothelial dysfunction. Alpha-glucosidase inhibitors (α-GIs) improve postprandial hyperglycemia (PPHG) and may have favorable effects on associated cardiovascular disease. Effects of α-GIs in patients with acute coronary syndrome (ACS) and PPHG remain unclear; thus, we assessed the effect of α-GI miglitol on endothelial function in such patients by digital reactive hyperemia peripheral arterial tonometry (RH-PAT). Methods Fifty-four patients with ACS who underwent primary percutaneous coronary intervention were enrolled in the study: 36 with new-onset PPHG and 18 with normal glucose tolerance. Eighteen PPHG patients were given 50 mg of miglitol with each meal for 1 week. Endothelial function was assessed on the basis of the RH-PAT index (RHI) before and after the 1-week miglitol treatment. The other 18 PPHG patients and the 18 NGT patients were not given any anti-diabetic agent for 1 week, and endothelial function was assessed. Results Postprandial RHI decreased significantly in patients with PPHG. Miglitol improved PPHG significantly; postprandial RHI also improved (p = 0.007). Significant inverse correlation was found between the postprandial change in RHI and postprandial fasting-to-60-minutes surge in glucose (r = -0.382, p = 0.009). Moreover, the improvement in endothelial function correlated with the reduced postprandial glucose surge achieved with miglitol (r = -0.462, p = 0.001). Conclusions Postprandial changes in glucose are related to endothelial dysfunction in ACS. Miglitol-based improvement in PPHG appears to improve endothelial function. The effect of miglitol on glucose-dependent endothelial function might improve outcomes of ACS. PMID:23777506

  7. Vaginal Heparan Sulfate Linked to Neutrophil Dysfunction in the Acute Inflammatory Response Associated with Experimental Vulvovaginal Candidiasis

    PubMed Central

    Yano, Junko; Noverr, Mairi C.

    2017-01-01

    ABSTRACT Despite acute inflammation by polymorphonuclear neutrophils (PMNs) during vulvovaginal candidiasis (VVC), clearance of Candida fails to occur. The purpose of this study was to uncover the mechanism of vaginal PMN dysfunction. Designs included assessing PMN migration, proinflammatory mediators, and tissue damage (by analysis of the activity of lactate dehydrogenase [LDH]) in mice susceptible (C3H/HeN-C57BL/6) or resistant (CD-1) to chronic VVC (CVVC-S or CVVC-R) and testing morphology-specific Candida albicans strains under conditions of preinduced PMN migration (CVVC-S mice) or PMN depletion (CVVC-R mice). In vitro designs included evaluation of C. albicans killing by elicited vaginal or peritoneal PMNs in standard or vaginal conditioned medium (VCM). Results showed that despite significant migration of PMNs and high levels of vaginal beta interleukin-1 (IL-1β) and alarmin S100A8, CVVC-S mice failed to reduce vaginal fungal burden irrespective of morphology or whether PMNs were present pre- or postinoculation, and had high LDH levels. In contrast, CVVC-R mice had reduced fungal burden and low LDH levels following PMN recruitment and IL-1β/S100A8 production, but maintained colonization in the absence of PMNs. Elicited vaginal and peritoneal PMNs showed substantial killing activity in standard media or VCM from CVVC-R mice but not in VCM from CVVC-S mice. The inhibitory effect of VCM from CVVC-S mice was unaffected by endogenous or exogenous estrogen and was ablated following depletion/neutralization of Mac-1 ligands using Mac-1+/+ PMNs or recombinant Mac-1. Heparan sulfate (HS) was identified as the putative inhibitor as evidenced by the rescue of PMN killing following heparanase treatment of VCM, as well as by inhibition of killing by purified HS. These results suggest that vaginal HS is linked to PMN dysfunction in CVVC-S mice as a competitive ligand for Mac-1. PMID:28292981

  8. Sepsis, systemic inflammatory response, and multiple organ dysfunction: the mystery continues.

    PubMed

    Fry, Donald E

    2012-01-01

    Human sepsis is thought to be systemic inflammatory response syndrome (SIRS) that is activated by invasive infection. The multiple organ dysfunction syndrome (MODS) is the identified failure of critical organ function in patients that have sustained SIRS. Because SIRS and MODS are consequences of the excessive activation of inflammation, extensive research and numerous clinical trials have pursued treatments that would modify the inflammatory response. This presentation reviews the normal local mechanisms of inflammation and provides a theoretical framework for the transition of the inflammatory process to a systemic level. Clinical trials with biomodulators to block or inhibit inflammation have generally failed to improve the outcomes in patients with severe sepsis, septic shock, and MODS. The role of counter-inflammatory signaling and the newer concept of the cholinergic anti-inflammatory pathway are being investigated, and newer hypotheses are focusing upon the balancing of proinflammatory and counter-inflammatory mechanisms as important directions for newer therapies. It is concluded that failure to define novel and effective treatments reflects fundamental gaps in our understanding of inflammation and its regulation.

  9. Estimation of right ventricular dysfunction by computed tomography pulmonary angiography: a valuable adjunct for evaluating the severity of acute pulmonary embolism.

    PubMed

    Jia, Dong; Zhou, Xiao-Ming; Hou, Gang

    2017-02-01

    To evaluate the feasibility and the efficacy of computed tomography pulmonary angiography (CTPA) in differentiating acute pulmonary embolism (PE) patients with or without right ventricular dysfunction and to evaluate the severity of right ventricular dysfunction in acute PE patients with CPTA. We retrospectively collected and measured the following parameters: right ventricular diameter by short axis in the axial plane (RVDaxial), left ventricular diameter by short axis in the axial plane (LVDaxial), right ventricular diameter by level on the reconstructed four-chamber views (RVD4-CH), left ventricular diameter by level on the reconstructed four-chamber views (LVD4-CH), main pulmonary artery diameter (MPAD), ascending aorta diameter (AOD), coronary sinus diameter (CSD), superior vena cava diameter (SVCD), inferior vena cava (IVC) reflux and interventricular septum deviation by CTPA, and we calculated the RVDaxial/LVDaxial, RVD4-CH/LVD4-CH and MPAD/AOD ratios in acute PE patients. We assessed right ventricular function and pulmonary artery systolic pressure (PASP) by echocardiography (ECHO) and then divided the patients into two groups: group A had right ventricular dysfunction, and group B did not have right ventricular dysfunction. We utilized a logistic regression model to analyse the relationship between right ventricular dysfunction and the measurement parameters obtained from CTPA, and we constructed the ROC curve to confirm the optimal cut-off value of the statistically significant parameter in the logistic regression model. After an initial screening, 113 acute PE patients were enrolled in our study. Among them, 42 patients showed right ventricular dysfunction (37.2 %), and 71 patients showed no right ventricular dysfunction (62.8 %). The difference between the patients with right ventricular dysfunction and patients without right ventricular dysfunction was statistical significant in RVD4-CH/LVD4-CH ratio. Logistic regression model analysis revealed

  10. The role of ventilation-induced surfactant dysfunction and atelectasis in causing acute respiratory distress syndrome.

    PubMed

    Albert, Richard K

    2012-04-01

    This Pulmonary Perspective describes a new pathophysiologic scenario by which the acute respiratory distress syndrome (ARDS) might develop, summarizes the literature on which this new scenario is based, and discusses the resulting implications with respect to patient management. Rather than ARDS occurring as a result of the inflammatory response associated with predisposing risk factors, the proposed scenario theorizes that the initiating problem is atelectasis that develops as a result of a surfactant abnormality that is caused by spontaneous or mechanical ventilation, together with our current approaches to patient positioning and sedation. The proposed pathophysiology implies that ventilation-induced lung injury occurs before, and causes, ARDS (rather than developing after the fact and only serving to magnify the existing injury) and that some instances of ARDS are iatrogenic. If the proposed scenario is correct, it also implies that at least some instances of ARDS might be prevented by implementing a number of simple, safe modifications in patient care.

  11. Acute Reversal of Endothelial Dysfunction in the Elderly Following Antioxidant Consumption

    PubMed Central

    Wray, D. Walter; Nishiyama, Steven K.; Harris, Ryan A.; Zhao, Jia; McDaniel, John; Fjeldstad, Anette S.; Witman, Melissa A.H.; Ives, Stephen J.; Barrett-O’Keefe, Zachary; Richardson, Russell S.

    2012-01-01

    Aging is associated with a pro-oxidant state and a decline in endothelial function. Whether acute, enteral antioxidant treatment can reverse this decrement in vascular function is not well known. Flow-mediated vasodilation and reactive hyperemia were evaluated following consumption of either placebo or an oral antioxidant cocktail (Vitamin C, 1000mg; Vitamin E, 600 I.U.; Alpha-lipoic acid, 600 mg) in 87 healthy volunteers (42 young, 25 ± 1 yrs; 45 older, 71 ± 1 yrs) using a double-blind, crossover design. Blood velocity and brachial artery diameter (ultrasound Doppler) were assessed before and after 5-min forearm circulatory arrest. Serum markers of lipid peroxidation, total antioxidant capacity, endogenous antioxidant activity, and Vitamin C were assayed, and plasma nitrate, nitrite, and 3-nitrotyrosine were determined. In the placebo trial, an age-related reduction in brachial artery vasodilation was evident (young: 7.4 ± 0.6 %; older: 5.2 ± 0.4 %). Following antioxidant consumption, flow-mediated vasodilation improved in older subjects (5.2 ± 0.4 %, placebo: 8.2 ± 0.6 %, antioxidant) but declined in the young (7.4 ± 0.6 %, placebo; 5.8 ± 0.6 %, antioxidant). Reactive hyperemia was reduced with age, but antioxidant administration did not alter the response in either group. Together, these data demonstrate that antioxidant consumption acutely restores endothelial function in the elderly, while disrupting normal endothelium-dependent vasodilation in the young, and suggest that this age-related impairment is due, at least in part, to free radicals. PMID:22353612

  12. Critical role of c-jun N-terminal protein kinase in promoting mitochondrial dysfunction and acute liver injury

    PubMed Central

    Jang, Sehwan; Yu, Li-Rong; Abdelmegeed, Mohamed A.; Gao, Yuan; Banerjee, Atrayee; Song, Byoung-Joon

    2015-01-01

    The mechanism by which c-Jun N-terminal protein kinase (JNK) promotes tissue injury is poorly understood. Thus we aimed at studying the roles of JNK and its phospho-target proteins in mouse models of acute liver injury. Young male mice were exposed to a single dose of CCl4 (50 mg/kg, IP) and euthanized at different time points. Liver histology, blood alanine aminotransferase, and other enzyme activities were measured in CCl4-exposed mice without or with the highly-specific JNK inhibitors. Phosphoproteins were purified from control or CCl4-exposed mice and analyzed by differential mass-spectrometry followed by further characterizations of immunoprecipitation and activity measurements. JNK was activated within 1 h while liver damage was maximal at 24 h post-CCl4 injection. Markedly increased phosphorylation of many mitochondrial proteins was observed between 1 and 8 h following CCl4 exposure. Pretreatment with the selective JNK inhibitor SU3327 or the mitochondria-targeted antioxidant mito-TEMPO markedly reduced the levels of p-JNK, mitochondrial phosphoproteins and liver damage in CCl4-exposed mice. Differential proteomic analysis identified many phosphorylated mitochondrial proteins involved in anti-oxidant defense, electron transfer, energy supply, fatty acid oxidation, etc. Aldehyde dehydrogenase, NADH-ubiquinone oxidoreductase, and α-ketoglutarate dehydrogenase were phosphorylated in CCl4-exposed mice but dephosphorylated after SU3327 pretreatment. Consistently, the suppressed activities of these enzymes were restored by SU3327 pretreatment in CCl4-exposed mice. These data provide a novel mechanism by which JNK, rapidly activated by CCl4, promotes mitochondrial dysfunction and acute hepatotoxicity through robust phosphorylation of numerous mitochondrial proteins. PMID:26491845

  13. Ventricular Dysfunction in Patients with Acute Coronary Syndrome Undergoing Coronary Surgical Revascularization: Prognostic Impact on Long-Term Outcomes

    PubMed Central

    Popovic, Batric; Agrinier, Nelly; Voilliot, Damien; Elfarra, Mazen; Villemot, Jean Pierre; Maureira, Pablo

    2016-01-01

    Background Patients with non-ST elevation acute coronary syndrome complicated by left ventricular dysfunction (LVEF) are a poor prognosis group. The aim of our study was to assess the short and long term LEVF prognostic value in a cohort of NSTE-ACS patients undergoing surgical revascularization. Methods We performed elective and isolated CABG on a cohort of 206 consecutive patients with LVEF≤0.40 complicating acute coronary syndrome. The case cohort was compared with a cohort of controls (LVEF>0.40) randomly selected (2:1) among patients who underwent the procedure during this period. Results The Kaplan-Meier 5-year estimated survival rates for patients in the low and normal LVEF groups were 70.8% (95% confidence interval CI: 64.2–77.4) and 81.7% (95%CI: 77.8–85.6), respectively. A low LVEF was associated with both a higher all-cause (HR [95%CI] = 1.84[1.18–2.86]) and a higher cardiovascular mortality (HR = 2.07 [1.27–3.38]) during the first 12 months of follow-up. After adjustment for potential confounders, a low LVEF remained associated with a higher cardiovascular mortality only (1.87[1.03–3.38]) during the first 12 months of follow-up. After 12 months of follow-up, a low LVEF was no more associated with all-cause, nor cardiovascular mortality. Conclusion Patients with low LVEF might require more intensive care than patients with normal LVEF during the year after the surgical procedure, but once the first postoperative year over, the initial low LVEF was no more associated with long term mortality. PMID:28005944

  14. Inhibition of IκB Kinase Attenuates the Organ Injury and Dysfunction Associated with Hemorrhagic Shock.

    PubMed

    Sordi, Regina; Chiazza, Fausto; Johnson, Florence L; Patel, Nimesh S A; Brohi, Karim; Collino, Massimo; Thiemermann, Christoph

    2015-06-18

    Nuclear factor-kappa B (NF-κB) activation is widely implicated in multiple organ failure (MOF); however, a direct inhibitor of IκB kinase (IKK), which plays a pivotal role in the activation of NF-κB, has not been investigated in shock. Thus, the aim of the present work was to investigate the effects of an IKK inhibitor on the MOF associated with hemorrhagic shock (HS). Therefore, rats were subjected to HS and were resuscitated with the shed blood. Rats were treated with the inhibitor of IKK or vehicle at resuscitation. Four hours later, blood and organs were assessed for organ injury and signaling events involved in the activation of NF-κB. Additionally, survival following serum deprivation was assessed in HK-2 cells treated with the inhibitor of IKK. HS resulted in renal dysfunction, lung, liver and muscular injury, and increases in serum inflammatory cytokines. Kidney and liver tissue from HS rats revealed increases in phosphorylation of IKKαβ and IκBα, nuclear translocation of NF-κB and expression of inducible isoform of nitric oxide synthase (iNOS). IKK16 treatment upon resuscitation attenuated NF-κB activation and activated the Akt survival pathway, leading to a significant attenuation of all of the above parameters. Furthermore, IKK16 exhibited cytoprotective effects in human kidney cells. In conclusion, the inhibitor of IKK complex attenuated the MOF associated with HS. This effect may be due to the inhibition of the NF-κB pathway and activation of the survival kinase Akt. Thus, the inhibition of the IKK complex might be an effective strategy for the prevention of MOF associated with HS.

  15. Inhibition of IκB Kinase Attenuates the Organ Injury and Dysfunction Associated with Hemorrhagic Shock

    PubMed Central

    Sordi, Regina; Chiazza, Fausto; Johnson, Florence L; Patel, Nimesh S A; Brohi, Karim; Collino, Massimo; Thiemermann, Christoph

    2015-01-01

    Nuclear factor-kappa B (NF-κB) activation is widely implicated in multiple organ failure (MOF); however, a direct inhibitor of IκB kinase (IKK), which plays a pivotal role in the activation of NF-κB, has not been investigated in shock. Thus, the aim of the present work was to investigate the effects of an IKK inhibitor on the MOF associated with hemorrhagic shock (HS). Therefore, rats were subjected to HS and were resuscitated with the shed blood. Rats were treated with the inhibitor of IKK or vehicle at resuscitation. Four hours later, blood and organs were assessed for organ injury and signaling events involved in the activation of NF-κB. Additionally, survival following serum deprivation was assessed in HK-2 cells treated with the inhibitor of IKK. HS resulted in renal dysfunction, lung, liver and muscular injury, and increases in serum inflammatory cytokines. Kidney and liver tissue from HS rats revealed increases in phosphorylation of IKKαβ and IκBα, nuclear translocation of NF-κB and expression of inducible isoform of nitric oxide synthase (iNOS). IKK16 treatment upon resuscitation attenuated NF-κB activation and activated the Akt survival pathway, leading to a significant attenuation of all of the above parameters. Furthermore, IKK16 exhibited cytoprotective effects in human kidney cells. In conclusion, the inhibitor of IKK complex attenuated the MOF associated with HS. This effect may be due to the inhibition of the NF-κB pathway and activation of the survival kinase Akt. Thus, the inhibition of the IKK complex might be an effective strategy for the prevention of MOF associated with HS. PMID:26101953

  16. Acute and chronic endothelial dysfunction: implications for the development of heart failure.

    PubMed

    Linke, Axel; Recchia, Fabio; Zhang, Xiaoping; Hintze, Thomas H

    2003-01-01

    Heart failure has been characterized by a reduction in cardiac contractile function resulting in reduced cardiac output. The clinical symptoms including mild tachycardia, reduced arterial pressure, increased venous or filling pressure and exercise intolerance have conceptually, to a large degree, been attributed to cardiac myocyte dysfunction. More recently, a vascular component has been recognized to contribute to heart failure. Among the most studied vascular mechanisms that might contribute to the development of heart failure has been the reduced production of nitric oxide or the reduced bioactivity of NO associated with both basic models of heart failure and disease in patients. The still evolving concept that heart failure is a cytokine activated state has, in addition, focused attention on the possibility that the cytokine driven isoform of NO synthase (NOS), iNOS, may produce sufficient quantities of NO to actually suppress cardiac myocyte function contributing to the reduced inotropic state in the failing heart. Thus, our view of the role of NO in the development of heart failure has evolved from simply a reduction in production of NO in blood vessels, to altered substrate availability (i.e. L-arginine), to increased scavenging of NO by superoxide anion, to increased production of NO from iNOS. As these concepts develop, our approach to the therapeutics of heart failure has also progressed with the recognition of the need to develop treatments directed towards addressing one or more of these etiologies. This review will focus on these aspects of the involvement of NO in the development of heart failure and some of the treatments that have developed from our understanding of the basic biology of NO to address these pathohysiologic states.

  17. SHOCK VOLUME: A PATIENT-SPECIFIC INDEX THAT PREDICTS TRANSFUSION REQUIREMENTS AND ORGAN DYSFUNCTION IN MULTIPLY INJURED PATIENTS.

    PubMed

    McKinley, Todd O; McCarroll, Tyler; Gaski, Greg E; Frantz, Travis L; Zarzaur, Ben L; Terry, Colin; Steenburg, Scott D

    2016-02-01

    Multiply injured patients (MIPs) in hemorrhagic shock develop oxygen debt which causes organ dysfunction and can lead to death. We developed a noninvasive patient-specific index, Shock Volume (SV), to quantify the magnitude of hypoperfusion. SV integrates the magnitude and duration that incremental shock index values are elevated above known thresholds of hypoperfusion using serial individual vital sign data. SV can be monitored in real time to assess ongoing hypoperfusion. The goal of this study was to determine how SV corresponded to transfusion requirements and organ dysfunction in a retrospective cohort of 74 MIPs. We measured SV in 6-h increments for 48 h after injury in multiply injured adults (18-65; Injury Severity Score ≥18). Patients who had accumulated 40 units of SV within 6 h of injury and 100 units of SV within 12 h of injury were at high risk for requiring massive transfusion or multiple critical administration transfusions. SV measurements were equally sensitive and specific as compared with base deficit values in predicting transfusions. SV measurements at 6 h after injury stratified patients at risk for multiple organ failure determined by Denver scores. In addition, SV values corresponded to the magnitude of organ failure determined by Sequential Organ Failure Assessment scores. SV is a patient-specific index that can be quantified in real time in critically injured patients. It is a surrogate for cumulative hypoperfusion and it predicts high-volume transfusions and organ dysfunction.

  18. Acute toxicity of saline produced waters to marine organisms

    SciTech Connect

    Pillard, D.A.; Evans, J.M.; DuFresne, D.L.

    1996-11-01

    Produced waters from oil and gas drilling operations are typically very saline, and may cause acute toxicity to marine organisms due imbalances as well as to an excess or deficiency of to osmotic specific common ions. In order to better understand the relationship between toxicity and ion concentration, laboratory toxicity tests were conducted using mysid shrimp (Mysidopsis bahia), sheepshead minnow, (Cyprinodon variegatus), and inland silvemide (Menidia beryllina). For each species the ionic concentration of standard laboratory water was proportionally increased or decreased to produce test solutions with a range of salinities. Individual ions (sodium, potassium, calcium, magnesium, strontium, chloride, bromide, sulfate, bicarbonate, and borate) were also manipulated to examine individual ion toxicity. Organisms were exposed for 48 hours. The three test species differ in their tolerance of salinity. Mysid shrimp show a marked decrease in survival at salinities less than approximately 5 ppt. Both fish species tolerated low salinity water, however, silversides were less tolerant of saline waters (salinity greater than 40 ppt). There were also significant differences in the responses of the organisms to different ions. The results show that salinity of the test solution may play an important role in the responses of the organisms to produced water effluent. Predictable toxicity/ion relationships developed in this study can be used to estimate whether toxicity in produced water is a result of common ions, salinity, or some other unknown toxicant.

  19. Olfactory dysfunction in acute rhinosinusitis: intranasal sodium hyaluronate as adjuvant treatment.

    PubMed

    Ciofalo, Andrea; de Vincentiis, Marco; Zambetti, Giampietro; Altissimi, Giancarlo; Fusconi, Massimo; Greco, Antonio; Ottaviano, Giancarlo; Magliulo, Giuseppe

    2017-02-01

    Acute rhinosinusitis (ARS) is defined as an inflammation of the mucosa of the nose and paranasal sinuses and affects 1-5 % of general population in Europe. Sinonasal diseases represent the main cause of smell alterations in adult patients and lead to mucosal congestion, increased quantity and density of secretions and altered mucociliary transport. For this reason the odorous molecules contained in the inspired air, cannot interact with the olfactory epithelium. Medical therapy of ARS has to reduce the severity and duration of symptoms and prevent complications. Recent studies have shown that Sodium hyaluronate modulate inflammation and has a reparative effect on the nasal mucosa. 48 patients affected by acute rhinosinusitis proven by CT scan, were enrolled. They were submitted to nasal endoscopy, olfactometric and mucociliary transport evaluation (MCTt), Visual Analogue Scale Questionnaire (VAS) at T0, after 14-18 days (T1) and after 30-35 days (T2). The patients were randomized into two treatment groups, A and B, and were treated for 30 days; each group was composed of 24 subjects. All patients received Levofloxacin (500 mg for 10 days) and Prednisone (50 mg for 8 days, 25 mg for 4 days and 12, 5 mg for 4 days). Moreover, Group A received twice a day for 30 days high molecular weight Sodium Hyaluronate (3 %) plus saline solution (3 mL sodium chloride-NaCl-0.9 %) using a nebulizer ampoule for nasal douche. Group B received twice a day for 30 days saline solution (6 mL sodium chloride-NaCl-0.9 %) using a nebulizer ampoule for nasal douche. At T1 Group A shown lower values in MCTt and threshold score was significantly higher than in Group B. VAS showed statistically significant differences between the two groups, in particular for smell, nasal obstruction and for nasal discharge. At T2 Group A MCTt was significantly lower than in Group B; odour threshold improved in both groups but in Group A was still significantly higher than in Group B. No

  20. Adrenoceptor hyporeactivity is responsible for Escherichia coli endotoxin-induced acute vascular dysfunction in humans.

    PubMed

    Pleiner, Johannes; Heere-Ress, Elisabeth; Langenberger, Herbert; Sieder, Anna E; Bayerle-Eder, Michaela; Mittermayer, Fritz; Fuchsjäger-Mayrl, Gabriele; Böhm, Johannes; Jansen, Burkhard; Wolzt, Michael

    2002-01-01

    Impaired response to catecholamines contributes to the altered hemodynamics in sepsis, which has been attributed to excessive NO formation. We have studied the systemic hemodynamic and local forearm responses and inducible NO synthase (iNOS) expression during experimental endotoxemia in humans. Escherichia coli endotoxin (lipopolysaccharide [LPS]) was administered at doses of 1 or 2 ng/kg to healthy volunteers. In 10 subjects, the systemic pressor effect of phenylephrine was assessed before and after the administration of LPS. In 9 further subjects, forearm blood flow responses to intra-arterial noradrenaline, acetylcholine, glyceryl trinitrate, and N(G)-monomethyl-L-arginine (L-NMMA) were studied at baseline and after LPS administration. Peripheral blood was collected and analyzed for iNOS mRNA and protein. Four hours after LPS, the response of systolic blood pressure (P<0.0005) and heart rate (P<0.05) to phenylephrine was significantly reduced. In the forearm, noradrenaline-induced vasoconstriction was also reduced by approximately 50% (P<0.01), but L-NMMA responsiveness was unchanged. iNOS mRNA or protein was not increased. Marked vascular adrenoceptor hyporeactivity is detectable in the absence of increased NO activity or iNOS expression in endotoxemia, arguing against major involvement of vascular iNOS activity in the acute systemic vasodilation to LPS.

  1. Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study

    PubMed Central

    Blanco, Jesús; Muriel-Bombín, Arturo; Sagredo, Víctor; Taboada, Francisco; Gandía, Francisco; Tamayo, Luís; Collado, Javier; García-Labattut, Ángel; Carriedo, Demetrio; Valledor, Manuel; De Frutos, Martín; López, María-Jesús; Caballero, Ana; Guerra, José; Álvarez, Braulio; Mayo, Agustín; Villar, Jesús

    2008-01-01

    Introduction Sepsis is a leading cause of admission to non-cardiological intensive care units (ICUs) and the second leading cause of death among ICU patients. We present the first extensive dataset on the epidemiology of severe sepsis treated in ICUs in Spain. Methods We conducted a prospective, observational, multicentre cohort study, carried out over two 3-month periods in 2002. Our aims were to determine the incidence of severe sepsis among adults in ICUs in a specific area in Spain, to determine the early (48 h) ICU and hospital mortality rates, as well as factors associated with the risk of death. Results A total of 4,317 patients were admitted and 2,619 patients were eligible for the study; 311 (11.9%) of these presented at least 1 episode of severe sepsis, and 324 (12.4%) episodes of severe sepsis were recorded. The estimated accumulated incidence for the population was 25 cases of severe sepsis attended in ICUs per 100,000 inhabitants per year. The mean logistic organ dysfunction system (LODS) upon admission was 6.3; the mean sepsis-related organ failure assessment (SOFA) score on the first day was 9.6. Two or more organ failures were present at diagnosis in 78.1% of the patients. A microbiological diagnosis of the infection was reached in 209 episodes of sepsis (64.5%) and the most common clinical diagnosis was pneumonia (42.8%). A total of 169 patients (54.3%) died in hospital, 150 (48.2%) of these in the ICU. The mortality in the first 48 h was 14.8%. Factors associated with early death were haematological failure and liver failure at diagnosis, acquisition of the infection prior to ICU admission, and total LODS score on admission. Factors associated with death in the hospital were age, chronic alcohol abuse, increased McCabe score, higher LODS on admission, ΔSOFA 3-1 (defined as the difference in the total SOFA scores on day 3 and on day 1), and the difference of the area under the curve of the SOFA score throughout the first 15 days. Conclusions We

  2. Predictors of Long-Term Survival in Acute Coronary Syndrome Patients With Left Ventricular Dysfunction After Percutaneous Coronary Intervention

    PubMed Central

    Lee, Doo Hwan; Rhee, Jung Ae; Choi, Jin Su; Lee, Ki Hong; Lee, Min Goo; Sim, Doo Sun; Park, Keun-Ho; Yoon, Nam Sik; Yoon, Hyun Ju; Kim, Kye Hun; Park, Hyung Wook; Hong, Young Joon; Kim, Ju Han; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun; Kang, Jung Chaee

    2012-01-01

    Background and Objectives Predictive factors of mortality in acute coronary syndrome (ACS) patients with left ventricular dysfunction were analyzed during 5-year clinical follow-up after percutaneous coronary intervention (PCI). Subjects and Methods A total of 329 ACS consecutive patients (64.6±11.3 years, 227 males) who underwent PCI from January 2001 to March 2006 were followed for 5 years. All patients had lower than 40% of left ventricular ejection fraction (LVEF). Patients were divided into Group I (survived longer than 5-years: n=130, 101 males) and Group II (survived shorter than 5 years: n=199, 126 males). Results The cumulative survival rate was 88.0% at 1 month, 78.0% at 6 months, 75.0% at 1 year, 67.0% at 2 years, 62.0% at 3 years, 57.0% at 4 years and 40% at 5-years. Group II was older (61.6±11.2 years vs. 66.4±11.4 years, p<0.001), and showed higher prevalence of female gender (28.4% vs. 36.7%, p=0.006) and lower LVEF (35.3±5.2 vs. 33.6±5.6) than Group I. The independent predictors for mortality were LVEF <30% {odds ratio (OR)=1.793, 95% confidence interval (CI): 1.234-2.452, p=0.002}, serum creatinine >3.0 mg/dL (OR=2.455, 95% CI: 1.306-4.614, p=0.005), older than 65 years (OR=1.594, 95% CI: 1.152-2.206, p=0.005), and female gender (OR=1.524, 95% CI: 1.090-2.130, p=0.014). Conclusion Five-year survival rate was 40% in ACS patients with left ventricular dysfunction, and the predictors for mortality were low LVEF, high serum creatinine, old age, and female gender. PMID:23170097

  3. Renal Dysfunction was an Independent Predictor of In-Hospital Death and Ventricular Rupture in Patients With Acute Myocardial Infarction

    PubMed Central

    Goto, Masayuki; Oda, Eiji; Matsushita, Hirooki; Takarada, Ken; Tomita, Makoto; Saito, Atsushi; Fuse, Koichi; Fujita, Satoru; Ikeda, Yoshio; Kitazawa, Hitoshi; Takahashi, Minoru; Sato, Masahito; Okabe, Masaaki; Aizawa, Yoshifusa

    2012-01-01

    Background Apart from the severity of myocardial infarction and coronary artery disease, several predictors of in-hospital death (In-HD) are suggested in patients with acute myocardial infarction (AMI). Methods We investigated predictors of In-HD and ventricular rupture (VR) including ventricular septal rupture (VSR) and free wall rupture (FWR) with stepwise multivariable logistic regressions in 1,042 patients admitted to our Cardiovascular Center within 48 hours from symptom onset for the first attack of AMI. Results In-HD, VSR, and FWR were observed in 78 cases (7.5%), 14 cases of which 13 cases were In-HD, and 13 cases of which 6 cases were In-HD, respectively. Apart from the disease severity, age and renal dysfunction (RD) defined by estimated glomerular filtration rate of lower than 60 mL/min/ 1.73 m2 were independent positive predictors of In-HD (the odds ratios (ORs) (95% confidence interval (CI)): 1.04 (1.01 - 1.06) P = 0.0069 and 5.75 (3.12 - 10.59) P < 0.0001, respectively) and hypercholesterolemia was an independent negative predictor for In-HD (OR (95% CI): 0.34 (0.17 - 0.67) P = 0.0017). After including the categories of coronary disease, ventricular rupture, and ejection fraction in predictors, RD remained an independent predictor of In-HD (OR (95% CI): 6.65 (2.67 - 16.60) P < 0.0001). Age (OR (95% CI): 1.07 (1.02 - 1.12) P = 0.0064), RD (OR (95% CI): 2.77 (1.18 - 6.49) P = 0.019), and diabetes (OR (95% CI): 2.52 (1.12 - 5.71) P = 0.026) were independent predictors of VR. Conclusions RD was an independent predictor of In-HD and VR in patients with initial AMI.

  4. Relationship between expression of triggering receptor-1 on myeloid cells in intestinal tissue and intestinal barrier dysfunction in severe acute pancreatitis

    PubMed Central

    Yin, Kai; Dang, Sheng-chun; Zhang, Jian-xin

    2011-01-01

    BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) in the intestine was upregulated and correlated with disease activity in inflammatory bowel diseases. Membrane-bound TREM-1 protein is increased in the pancreas, liver and kidneys of patients with severe acute pancreatitis (SAP), suggesting that TREM-1 may act as an important mediator of inflammation and subsequent extra-pancreatic organ injury. This study aimed to investigate the relationship between the expression of TREM-1 in intestinal tissue and intestinal barrier dysfunction in SAP. METHODS: Sixty-four male Wistar rats were randomly divided into a sham operation group (SO group, n=32) and a SAP group (n=32). A SAP model was established by retrograde injection of 5% sodium deoxycholate into the bile-pancreatic duct. Specimens were taken from blood and intestinal tissue 2, 6, 12, and 48 hours after operation respectively. The levels of D-lactate, diamine oxidase (DAO) and endotoxin in serum were measured using an improved spectro-photometric method. The expression levels of TREM-1, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) mRNA in terminal ileum were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). Specimens of the distal ileum were taken to determine pathological changes by a validated histology score. RESULTS: The serum levels of D-lactate, DAO and endotoxin were significantly increased in each subgroup of SAP compared with the SO group (P<0.01, P<0.05). The expression levels of TREM-1, IL-1β and TNF-α mRNA in the terminal ileum in each subgroup of SAP were significantly higher than those in the SO group (P<0.01, P<0.05). The expression level of TREM-1mRNA was positively correlated with IL-1β and TNF-α mRNA (r=0.956, P=0.044; r=0.986, P=0.015), but the correlation was not found between IL-1β mRNA and TNF-α mRNA (P=0.133). Compared to the SO group, the pathological changes were aggravated significantly in the SAP group. CONCLUSIONS

  5. Acute toxicity of biodiesel to freshwater and marine organisms

    SciTech Connect

    Reece, D.; Peterson, C.

    1995-11-01

    Biodiesel fuels are reported to be nontoxic resulting in less potential hazard to fish and other aquatic life in case of accidental spills. This paper reports on static tests with rapeseed methyl ester (RME) and rapeseed ethyl ester (REE) performed according to EPA/600/4-90/027. The acute aquatic toxicity tests were conducted with both rainbow trout and daphnia magna by CH2M Hill in Corvallis, Oregon under contract to the University of Idaho. The LC50 (the point at which 50% have died and 50% are still alive determined by interpolation) values for each of the substrates tested with daphnia magna in parts per million were as follows: control(table salt (NaCl)) = 3.7, D2 = 1.43, RME = 23, REE = 99, and Methyl Soyate = 332. Duplicate tests with rainbow trout were run with 10 organisms per replicate. LC50 numbers were not reported because of the failure to kill a sufficient number of fish at the concentrations tested, even with the diesel control fuel. The 20 percent and 50 percent blends had scattered losses of fish but none of the tests had less than 85 percent survival at any concentrations after 96 hours.

  6. Erectile dysfunction

    PubMed Central

    Yafi, Faysal A.; Jenkins, Lawrence; Albersen, Maarten; Corona, Giovanni; Isidori, Andrea M.; Goldfarb, Shari; Maggi, Mario; Nelson, Christian J.; Parish, Sharon; Salonia, Andrea; Tan, Ronny; Mulhall, John P.; Hellstrom, Wayne J. G.

    2016-01-01

    Erectile dysfunction is a multidimensional but common male sexual dysfunction that involves an alteration in any of the components of the erectile response, including organic, relational and psychological. Roles for nonendocrine (neurogenic, vasculogenic and iatrogenic) and endocrine pathways have been proposed. Owing to its strong association with metabolic syndrome and cardiovascular disease, cardiac assessment may be warranted in men with symptoms of erectile dysfunction. Minimally invasive interventions to relieve the symptoms of erectile dysfunction include lifestyle modifications, oral drugs, injected vasodilator agents and vacuum erection devices. Surgical therapies are reserved for the subset of patients who have contraindications to these nonsurgical interventions, those who experience adverse effects from (or are refractory to) medical therapy and those who also have penile fibrosis or penile vascular insufficiency. Erectile dysfunction can have deleterious effects on a man’s quality of life; most patients have symptoms of depression and anxiety related to sexual performance. These symptoms, in turn, affect his partner’s sexual experience and the couple’s quality of life. This Primer highlights numerous aspects of erectile dysfunction, summarizes new treatment targets and ongoing preclinical studies that evaluate new pharmacotherapies, and covers the topic of regenerative medicine, which represents the future of sexual medicine. PMID:27188339

  7. Cerebral Dysfunctions Related to Perinatal Organic Damage: Clinical-Neuropathologic Correlations.

    ERIC Educational Resources Information Center

    Towbin, Abraham

    1978-01-01

    Recent neuropathology studies identify hypoxia as the main cause of perinatal cerebral damage. Cerebral lesions present at birth, with transition to chronic scar lesions, are correlated to mental retardation, cerebral palsy, epilepsy, and minimal brain dysfunction. Gestation age and severity of hypoxic exposure essentially determine the cerebral…

  8. Increased risk of organic erectile dysfunction in patients with chronic fatigue syndrome: a nationwide population-based cohort study.

    PubMed

    Chao, C-H; Chen, H-J; Wang, H-Y; Li, T-C; Kao, C-H

    2015-07-01

    Chronic fatigue syndrome (CFS) is a complex disorder characterized by profound and persistent fatigue and several comorbidities. CFS was previously reported to be associated with female sexual dysfunction. We propose that CFS might also be associated with organic erectile dysfunction (organic ED). We conducted a retrospective cohort study by using data from the National Health Insurance (NHI) Research Database. We identified 2156 male patients who were newly diagnosed with CFS between January 1, 2003 and December 31, 2006. After excluding those younger than 20 years and prevalent cases, 1976 patients were subjected to analysis, and 7904 people served as healthy controls. All study subjects were followed up from the index date to the date of organic ED diagnosis, withdrawal from the NHI program, or the end of 2011. Compared with the non-CFS cohort, the incidence density rate of organic ED was 1.88-fold higher than that in the CFS cohort (3.23 vs. 1.73 per 1000 person-years) with an adjusted hazard ratio (HR) of 1.88 (95% CI = 1.26-2.81) when adjusting for sex and comorbidities. The combined impacts of patients with CFS and cardiovascular disease (CVD), diabetes mellitus (DM), chronic kidney disease (CKD), depression, and anxiety showed a significant by joint association with organic ED risk compared with patients with no CFS and no counterpart comorbidity. The greatest magnitude of adjusted HR of ED for CFS was observed in individuals without any comorbidity (3.87, 1.95-7.66). The incidence of organic ED is higher among males aged 40 years and over for both CFS and non-CFS cohorts. As the number of comorbidity increases, the incidence of organic ED increases in males without CFS. Higher incidence of organic ED was observed in males with CVD, DM, CKD, depression, or anxiety for both CFS and non-CFS cohorts.

  9. The multiple organ dysfunction syndrome caused by endotoxin in the rat: attenuation of liver dysfunction by inhibitors of nitric oxide synthase.

    PubMed Central

    Thiemermann, C.; Ruetten, H.; Wu, C. C.; Vane, J. R.

    1995-01-01

    1. We have investigated whether (i) endotoxaemia caused by E. coli lipopolysaccharide in the anaesthetized rat causes a multiple organ dysfunction syndrome (MODS; e.g. circulatory failure, renal failure, liver failure), and (ii) an enhanced formation of nitric oxide (NO) due to induction of inducible NO synthase (iNOS) contributes to the MODS. In addition, this study elucidates the beneficial and adverse effects of aminoethyl-isothiourea (AE-ITU), a relatively selective inhibitor of iNOS activity, and NG-methyl-L-arginine (L-NMMA), a non-selective inhibitor of NOS activity on the MODS caused by endotoxaemia. 2. In the anaesthetized rat, LPS caused a fall in mean arterial blood pressure (MAP) from 117 +/- 3 mmHg (time 0) to 97 +/- 4 mmHg at 2 h (P < 0.05, n = 15) and 84 +/- 4 mmHg at 6 h (P < 0.05, n = 15). The pressor effect of noradrenaline (NA, 1 micrograms kg-1, i.v.) was also significantly reduced at 1 to 6 h after LPS (vascular hyporeactivity). Treatment of LPS-rats with AE-ITU (1 mg kg-1, i.v. plus 1 mg kg-1 h-1 starting at 2 h after LPS) caused only a transient rise in MAP, but significantly attenuated the delayed vascular hyporeactivity seen in LPS-rats. Infusion of L-NMMA (3 mg kg-1, i.v. plus 3 mg kg-1 h-1) caused a rapid and sustained rise in MAP and attenuated the delayed vascular hyporeactivity to NA. Neither AE-ITU nor L-NMMA had any effect on either MAP or the pressor effect elicited by NA in rats infused with saline rather than LPS. 3. Endotoxaemia for 6 h was associated with a significant rise in the serum levels of aspartate or alanine aminotransferase (i.e. GOT or GPT), gamma-glutamyl-transferase (gamma GT), and bilirubin, and hence, liver dysfunction. Treatment of LPS-rats with AE-ITU significantly attenuated this liver dysfunction (rise in GOT, GPT, gamma GT and bilirubin) (P < 0.05, n = 10). In contrast, L-NMMA reduced the increase in the serum levels of gamma GT and bilirubin, but not in GOT and GPT (n = 5). Injection of LPS also caused a

  10. Pharmacological preconditioning with erythropoietin attenuates the organ injury and dysfunction induced in a rat model of hemorrhagic shock.

    PubMed

    Nandra, Kiran K; Collino, Massimo; Rogazzo, Mara; Fantozzi, Roberto; Patel, Nimesh S A; Thiemermann, Christoph

    2013-05-01

    Pre-treatment with erythropoietin (EPO) has been demonstrated to exert tissue-protective effects against 'ischemia-reperfusion'-type injuries. This protection might be mediated by mobilization of bone marrow endothelial progenitor cells (EPCs), which are thought to secrete paracrine factors. These effects could be exploited to protect against tissue injury induced in cases where hemorrhage is foreseeable, for example, prior to major surgery. Here, we investigate the effects of EPO pre-treatment on the organ injury and dysfunction induced by hemorrhagic shock (HS). Recombinant human EPO (1000 IU/kg/day i.p.) was administered to rats for 3 days. Rats were subjected to HS on day 4 (pre-treatment protocol). Mean arterial pressure was reduced to 35 ± 5 mmHg for 90 minutes, followed by resuscitation with 20 ml/kg Ringer's lactate for 10 minutes and 50% of the shed blood for 50 minutes. Rats were sacrificed 4 hours after the onset of resuscitation. EPC (CD34(+)/flk-1(+) cell) mobilization was measured following the 3-day pre-treatment with EPO and was significantly increased compared with rats pre-treated with phosphate-buffered saline. EPO pre-treatment significantly attenuated organ injury and dysfunction (renal, hepatic and neuromuscular) caused by HS. In livers from rats subjected to HS, EPO enhanced the phosphorylation of Akt (activation), glycogen synthase kinase-3β (GSK-3β; inhibition) and endothelial nitric oxide synthase (eNOS; activation). In the liver, HS also caused an increase in nuclear translocation of p65 (activation of NF-κB), which was attenuated by EPO. This data suggests that repetitive dosing with EPO prior to injury might protect against the organ injury and dysfunction induced by HS, by a mechanism that might involve mobilization of CD34(+)/flk-1(+) cells, resulting in the activation of the Akt-eNOS survival pathway and inhibition of activation of GSK-3β and NF-κB.

  11. Neuronal Nitric Oxide Synthase is Involved in Vascular Hyporeactivity and Multiple Organ Dysfunction Associated with Hemorrhagic Shock.

    PubMed

    Sordi, Regina; Chiazza, Fausto; Collino, Massimo; Assreuy, Jamil; Thiemermann, Christoph

    2016-05-01

    Severe hemorrhage can lead to global ischemia and hemorrhagic shock (HS), resulting in multiple organ failure (MOF) and death. Restoration of blood flow and re-oxygenation is associated with an exacerbation of tissue injury and inflammatory response. The neuronal nitric oxide synthase (nNOS) has been implicated in vascular collapse and systemic inflammation of septic shock; however, the role of nNOS in HS is poorly understood. The aim of this study was to evaluate the role of nNOS in the MOF associated with HS.Rats were subjected to HS under anesthesia. Mean arterial pressure was reduced to 30  mmHg for 90  min, followed by resuscitation with shed blood. Rats were randomly treated with two chemically distinct nNOS inhibitors [ARL 17477 (1 mg/kg) and 7-nitroindazol (5 mg/kg)] or vehicle upon resuscitation. Four hours later, parameters of organ injury and dysfunction were assessed.HS was associated with MOF development. Inhibition of nNOS activity at resuscitation protected rats against the MOF and vascular dysfunction. In addition, treatment of HS rats with nNOS inhibitors attenuated neutrophil infiltration into target organs and decreased the activation of NF-κB, iNOS expression, NO production, and nitrosylation of proteins. Furthermore, nNOS inhibition also reduced the levels of pro-inflammatory cytokines TNF-α and IL-6 in HS rats.In conclusion, two distinct inhibitors of nNOS activity reduced the MOF, vascular dysfunction, and the systemic inflammation associated with HS. Thus, nNOS inhibitors may be useful as an adjunct therapy before fluids and blood administration in HS patients to avoid the MOF associated with reperfusion injury during resuscitation.

  12. Heart Rate Variability in Patients with Acute Ischemic Stroke at Different Stages of Renal Dysfunction: A Cross-sectional Observational Study

    PubMed Central

    Wei, Lin; Zhao, Wen-Bo; Ye, Huan-Wen; Chen, Yan-Hua; Zhang, Xiao-Pei; Huang, Yan; Cai, Ye-Feng; Chen, Quan-Fu; Pan, Su-Yue

    2017-01-01

    Background: Renal function is associated with mortality and functional disabilities in stroke patients, and impaired autonomic function is common in stroke, but little is known regarding its effects on stroke patients with renal dysfunction. This study sought to evaluate the association between autonomic function and stroke in patients with renal dysfunction. Methods: This study comprised 232 patients with acute ischemic stroke consecutively enrolled from February 2013 to November 2014 at Guangdong Provincial Hospital of Chinese Medicine in China. All patients recruited underwent laboratory evaluation and 24 h Holter electrocardiography (ECG). Autonomic function was measured based on the heart rate variability (HRV) using 24 h Holter ECG. Renal damage was assessed through the estimated glomerular filtration rate (eGFR), and stroke severity was rated according to the National Institutes of Health Stroke Scale (NIHSS). The Barthel index and modified Rankin score were also determined following admission. All the clinical covariates that could potentially affect autonomic outcome variables were adjusted with linear regression. Results: In the patients with a mild or moderate decreased eGFR, the values for the standard deviation of the averaged normal-to-normal RR interval (SDANN) index (P = 0.022), very low frequency (VLF) (P = 0.043), low frequency (LF) (P = 0.023), and ratio of low-to-high frequency power (LF/HF) (P = 0.001) were significantly lower than those in the patients with a normal eGFR. A multinomial linear regression indicated that eGFR (t = 2.47, P = 0.014), gender (t = −3.60, P < 0.001), and a history of hypertension (t = −2.65, P = 0.008) were the risk factors of LF/HF; the NIHSS score (SDANN index: t = −3.83, P < 0.001; VLF: t = −3.07, P = 0.002; LF: t = −2.79, P = 0.006) and a history of diabetes (SDANN index: t = −3.58, P < 0.001; VLF: t = −2.54, P = 0.012; LF: t = −2.87, P = 0.004) were independent factors for the SDANN index, VLF

  13. Death receptor and mitochondria-mediated hepatocyte apoptosis underlies liver dysfunction in rats exposed to organic pollutants from drinking water.

    PubMed

    Yang, Guanghong; Zhou, Zhiwei; Cen, Yanli; Gui, Xiaolin; Zeng, Qibing; Ao, Yunxia; Li, Qian; Wang, Shiran; Li, Jun; Zhang, Aihua

    2015-01-01

    Persistent organic pollutants in drinking water impose a substantial risk to the health of human beings, but the evidence for liver toxic effect and the underlying mechanism is scarce. This study aimed to examine the liver toxicity and elucidate the molecular mechanism of organic pollutants in drinking water in normal human liver cell line L02 cells and rats. The data showed that organic extraction from drinking water remarkably impaired rat liver function, evident from the increase in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase, and decrease in the serum level of total protein and albumin. Organic extraction dose-dependently induced apoptotic cell death in rat liver and L02 cells. Administration of rats with organic extraction promoted death receptor signaling pathway through the increase in gene and protein expression level of Fas and FasL. Treatment of rats with organic extraction also induced mitochondria-mediated apoptosis via increasing the expression level of proapoptotic protein, Bax, but decreasing the expression level of antiapoptotic protein, Bcl-2, resulting in an upregulation of cytochrome c and activation of caspase cascade at both transcriptional and post-transcriptional levels. Moreover, organic extraction enhanced rat liver glutathione S-transferases activity and reactive oxygen species generation, and upregulated aryl hydrocarbon receptor and glutathione S-transferase A1 at both transcriptional and translational levels. Collectively, the results indicate that organic extraction from drinking water impairs liver function, with the involvement of death receptor and mitochondria-mediated apoptosis in rats. The results provide evidence and molecular mechanisms for organic pollutants in drinking water-induced liver dysfunction, which may help prevent and treat organic extraction-induced liver injury.

  14. Common Variants of TLR1 Associate with Organ Dysfunction and Sustained Pro-Inflammatory Responses during Sepsis

    PubMed Central

    Pino-Yanes, Maria; Corrales, Almudena; Casula, Milena; Blanco, Jesús; Muriel, Arturo; Espinosa, Elena; García-Bello, Miguel; Torres, Antoni; Ferrer, Miguel; Zavala, Elizabeth

    2010-01-01

    Background Toll-like receptors (TLRs) are critical components for host pathogen recognition and variants in genes participating in this response influence susceptibility to infections. Recently, TLR1 gene polymorphisms have been found correlated with whole blood hyper-inflammatory responses to pathogen-associated molecules and associated with sepsis-associated multiorgan dysfunction and acute lung injury (ALI). We examined the association of common variants of TLR1 gene with sepsis-derived complications in an independent study and with serum levels for four inflammatory biomarkers among septic patients. Methodology/Principal Findings Seven tagging single nucleotide polymorphisms of the TLR1 gene were genotyped in samples from a prospective multicenter case-only study of patients with severe sepsis admitted into a network of intensive care units followed for disease severity. Interleukin (IL)-1β, IL-6, IL-10, and C-reactive protein (CRP) serum levels were measured at study entry, at 48 h and at 7th day. Alleles -7202G and 248Ser, and the 248Ser-602Ile haplotype were associated with circulatory dysfunction among severe septic patients (0.001≤p≤0.022), and with reduced IL-10 (0.012≤p≤0.047) and elevated CRP (0.011≤p≤0.036) serum levels during the first week of sepsis development. Additionally, the -7202GG genotype was found to be associated with hospital mortality (p = 0.017) and ALI (p = 0.050) in a combined analysis with European Americans, suggesting common risk effects among studies. Conclusions/Significance These results partially replicate and extend previous findings, supporting that variants of TLR1 gene are determinants of severe complications during sepsis. PMID:21048935

  15. Acute toxicant exposure and cardiac autonomic dysfunction from smoking a single narghile waterpipe with tobacco and with a “healthy” tobacco-free alternative

    PubMed Central

    Cobb, Caroline O.; Sahmarani, Kamar; Eissenberg, Thomas; Shihadeh, Alan

    2012-01-01

    Tobacco smoking using a waterpipe (narghile, hookah, shisha) has become a global epidemic. Unlike cigarette smoking, little is known about the health effects of waterpipe use. One acute effect of cigarette smoke inhalation is dysfunction in autonomic regulation of the cardiac cycle, as indicated by reduction in heart rate variability (HRV). Reduced HRV is implicated in adverse cardiovascular health outcomes, and is associated with inhalation exposure-induced oxidative stress. Using a 32 participant cross-over study design, we investigated toxicant exposure and effects of waterpipe smoking on heart rate variability when, under controlled conditions, participants smoked a tobacco-based and a tobacco-free waterpipe product promoted as an alternative for “health-conscious” users. Outcome measures included HRV, exhaled breath carbon monoxide (CO), plasma nicotine, and puff topography, which were measured at times prior to, during, and after smoking. We found that waterpipe use acutely decreased HRV (p<0.01 for all measures), independent of product smoked. Plasma nicotine, blood pressure, and heart rate increased only with the tobacco-based product (p<0.01), while CO increased with both products (p<0.01). More smoke was inhaled during tobacco-free product use, potentially reflecting attempted regulation of nicotine intake. The data thus indicate that waterpipe smoking acutely compromises cardiac autonomic function, and does so through exposure to smoke constituents other than nicotine. PMID:23059956

  16. Inflammatory triggers of acute rejection of organ allografts

    PubMed Central

    Mori, Daniel N.; Kreisel, Daniel; Fullerton, James N.; Gilroy, Derek W.; Goldstein, Daniel R.

    2014-01-01

    Summary Solid organ transplantation is a vital therapy for end stage diseases. Decades of research has established that the components of the adaptive immune system are critical for transplant rejection, but the role of the innate immune system in organ transplantation is just emerging. Accumulating evidence indicates that the innate immune system is activated at the time of organ implantation by the release of endogenous inflammatory triggers. This review discusses the nature of these triggers in organ transplantation and also potential mediators that may enhance inflammation resolution after organ implantation. PMID:24517430

  17. Omega-9 Oleic Acid Induces Fatty Acid Oxidation and Decreases Organ Dysfunction and Mortality in Experimental Sepsis.

    PubMed

    Gonçalves-de-Albuquerque, Cassiano Felippe; Medeiros-de-Moraes, Isabel Matos; Oliveira, Flora Magno de Jesus; Burth, Patrícia; Bozza, Patrícia Torres; Castro Faria, Mauro Velho; Silva, Adriana Ribeiro; Castro-Faria-Neto, Hugo Caire de

    2016-01-01

    Sepsis is characterized by inflammatory and metabolic alterations, which lead to massive cytokine production, oxidative stress and organ dysfunction. In severe systemic inflammatory response syndrome, plasma non-esterified fatty acids (NEFA) are increased. Several NEFA are deleterious to cells, activate Toll-like receptors and inhibit Na+/K+-ATPase, causing lung injury. A Mediterranean diet rich in olive oil is beneficial. The main component of olive oil is omega-9 oleic acid (OA), a monounsaturated fatty acid (MUFA). We analyzed the effect of OA supplementation on sepsis. OA ameliorated clinical symptoms, increased the survival rate, prevented liver and kidney injury and decreased NEFA plasma levels in mice subjected to cecal ligation and puncture (CLP). OA did not alter food intake and weight gain but diminished reactive oxygen species (ROS) production and NEFA plasma levels. Carnitine palmitoyltransferase IA (CPT1A) mRNA levels were increased, while uncoupling protein 2 (UCP2) liver expression was enhanced in mice treated with OA. OA also inhibited the decrease in 5' AMP-activated protein kinase (AMPK) expression and increased the enzyme expression in the liver of OA-treated mice compared to septic animals. We showed that OA pretreatment decreased NEFA concentration and increased CPT1A and UCP2 and AMPK levels, decreasing ROS production. We suggest that OA has a beneficial role in sepsis by decreasing metabolic dysfunction, supporting the benefits of diets high in monounsaturated fatty acids (MUFA).

  18. Efficacy of N-Butylphthalide and Hyperbaric Oxygen Therapy on Cognitive Dysfunction in Patients with Delayed Encephalopathy After Acute Carbon Monoxide Poisoning

    PubMed Central

    Xiang, Wenping; Xue, Hui; Wang, Baojun; Li, Yuechun; Zhang, Jun; Jiang, Changchun; Pang, Jiangxia

    2017-01-01

    Background Delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) is one of the most serious complications after CO poisoning. This study was conducted to explore the efficacy of the combined application of N-Butylphthalide and hyperbaric oxygenation therapy (HBO) on cognitive dysfunction in patients with DEACMP. Material/Methods A total of 184 patients with DEACMP were randomly assigned to either receive HBO or N-Butylphthalide and HBO. Meanwhile, all patients received conventional treatment. The total remission rate (RR) was used to assess the clinical efficacy. The Mini-Mental State Examination (MMSE) was used to assess the cognitive function, and the National Institutes of Health Stroke Scale (NIHSS) was used to assess the neurological function. Results Finally, there were 90 and 94 patients in the control and experimental groups, respectively. After eight weeks of treatment, the total RR in the experimental group (47.9%) was significantly higher than that in the control group (33.3%). Compared to the control group, significantly more patients in the experimental group had MMSE scores of 24–30. The lower NIHSS score in the experimental group showed that N-Butylphthalide had the effect of preservation and restoration of neurological function. No obvious drug toxicity or liver and kidney dysfunction was observed, and there was no significant change in the level of blood glucose and blood lipids. Conclusions These results indicated that the combined application of N-Butylphthalide and HBO could significantly improve the cognitive dysfunction of patients with DEACMP and have great clinical efficacy, which should be further studied. PMID:28352069

  19. Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

    PubMed Central

    Delano, Matthew J.; Ward, Peter A.

    2016-01-01

    Sepsis is a systemic inflammatory response induced by an infection, leading to organ dysfunction and mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the interplay between inflammatory and antiinflammatory responses. With advances in intensive care management and goal-directed interventions, early sepsis mortality has diminished, only to surge later after “recovery” from acute events, prompting a search for sepsis-induced alterations in immune function. Sepsis is well known to alter innate and adaptive immune responses for sustained periods after clinical “recovery,” with immunosuppression being a prominent example of such alterations. Recent studies have centered on immune-modulatory therapy. These efforts are focused on defining and reversing the persistent immune cell dysfunction that is associated with mortality long after the acute events of sepsis have resolved. PMID:26727230

  20. Muscle organization in individuals with and without pain and joint dysfunction.

    PubMed

    Nickel, J C; Gonzalez, Y M; McCall, W D; Ohrbach, R; Marx, D B; Liu, H; Iwasaki, L R

    2012-06-01

    Central nervous system organization of masticatory muscles determines the magnitude of joint and muscle forces. Validated computer-assisted models of neuromuscular organization during biting were used to determine organization in individuals with and without temporomandibular disorders (TMD). Ninety-one individuals (47 women, 44 men) were assigned to one of four diagnostic groups based on the presence (+) or absence (-) of pain (P) and bilateral temporomandibular joint disc displacement (DD). Electromyography and bite-forces were measured during right and left incisor and molar biting. Two three-dimensional models employing neuromuscular objectives of minimization of joint loads (MJL) or muscle effort (MME) simulated biting tasks. Evaluations of diagnostic group and gender effects on choice of best-fit model were by analysis of variance (ANOVA) and Tukey-Kramer post hoc tests, evaluations of right-left symmetry were by Chi-square and Fisher's exact statistics, and evaluations of model accuracy were by within-subject linear regressions. MME was the best-fit during left molar biting in +DD individuals and incisor biting in men (all p < 0.03). Incisor biting symmetry in muscle organization was significantly higher (p < 0.03) in healthy individuals compared with those with TMD. Within-subject regressions showed that best-fit model errors were similar among groups: 8 to 15% (0.68 ≤ R(2) ≤ 0.74). These computer-assisted models predicted muscle organization during static biting in humans with and without TMDs.

  1. Muscle Organization in Individuals with and without Pain and Joint Dysfunction

    PubMed Central

    Nickel, J.C.; Gonzalez, Y.M.; McCall, W.D.; Ohrbach, R.; Marx, D.B.; Liu, H.; Iwasaki, L.R.

    2012-01-01

    Central nervous system organization of masticatory muscles determines the magnitude of joint and muscle forces. Validated computer-assisted models of neuromuscular organization during biting were used to determine organization in individuals with and without temporomandibular disorders (TMD). Ninety-one individuals (47 women, 44 men) were assigned to one of four diagnostic groups based on the presence (+) or absence (-) of pain (P) and bilateral temporomandibular joint disc displacement (DD). Electromyography and bite-forces were measured during right and left incisor and molar biting. Two three-dimensional models employing neuromuscular objectives of minimization of joint loads (MJL) or muscle effort (MME) simulated biting tasks. Evaluations of diagnostic group and gender effects on choice of best-fit model were by analysis of variance (ANOVA) and Tukey-Kramer post hoc tests, evaluations of right-left symmetry were by Chi-square and Fisher’s exact statistics, and evaluations of model accuracy were by within-subject linear regressions. MME was the best-fit during left molar biting in +DD individuals and incisor biting in men (all p < 0.03). Incisor biting symmetry in muscle organization was significantly higher (p < 0.03) in healthy individuals compared with those with TMD. Within-subject regressions showed that best-fit model errors were similar among groups: 8 to 15% (0.68 ≤ R2 ≤ 0.74). These computer-assisted models predicted muscle organization during static biting in humans with and without TMDs. PMID:22522774

  2. Correlation of quantitative tests of nerve and target organ dysfunction with skin immunohistology in leprosy.

    PubMed

    Facer, P; Mathur, R; Pandya, S S; Ladiwala, U; Singhal, B S; Anand, P

    1998-12-01

    Loss of nociception and hypohidrosis in skin are hallmarks of leprosy, attributed to early invasion by Mycobacterium leprae of Schwann cells related to unmyelinated nerve fibres. We have studied skin lesions and contralateral clinically unaffected skin in 28 patients across the leprosy spectrum with a range of selective quantitative sensory and autonomic tests, prior to biopsy of both sites. Unaffected sites showed normal skin innervation, when antibodies to the pan-neuronal marker PGP (protein gene product) 9.5 were used, with the exception of intraepidermal fibres which were not detected in the majority of cases. Elevation of thermal thresholds and reduced sensory axon-reflex flare responses in affected skin correlated with decreased nerve fibres in the subepidermis, e.g. axon-reflex flux units (means+/-SEM) for no detectable innervation; decreased innervation; and clinically unaffected skin, were 23+/-3.1; 41.2+/-7.3; and 84.5+/-4.0, respectively. Reduced nicotine-induced axon-reflex sweating was correlated with decreased innervation of sweat glands. Where methacholine-induced direct activation of sweat glands was affected, there was inflammatory infiltrate and loss of sweat gland structure. This study demonstrates a correlation between selective nerve dysfunction on clinical tests and morphological changes in skin, irrespective of the type of leprosy, and is the first to show that loss of sweating in leprosy may result either from decreased innervation and/or involvement of the sweat glands. The findings have implications for the selection and monitoring of patients with leprosy in clinical trials which aim to restore cutaneous function.

  3. Dysfunctional Attitudes Scale Perfectionism: A Predictor and Partial Mediator of Acute Treatment Outcome among Clinically Depressed Adolescents

    ERIC Educational Resources Information Center

    Jacobs, Rachel H.; Silva, Susan G.; Reinecke, Mark A.; Curry, John F.; Ginsburg, Golda S.; Kratochvil, Christopher J.; March, John S.

    2009-01-01

    The effect of perfectionism on acute treatment outcomes was explored in a randomized controlled trial of 439 clinically depressed adolescents (12-17 years of age) enrolled in the Treatment for Adolescents with Depression Study (TADS) who received cognitive behavior therapy (CBT), fluoxetine, a combination of CBT and FLX, or pill placebo. Measures…

  4. Memory Dysfunction

    PubMed Central

    Matthews, Brandy R.

    2015-01-01

    Purpose of Review: This article highlights the dissociable human memory systems of episodic, semantic, and procedural memory in the context of neurologic illnesses known to adversely affect specific neuroanatomic structures relevant to each memory system. Recent Findings: Advances in functional neuroimaging and refinement of neuropsychological and bedside assessment tools continue to support a model of multiple memory systems that are distinct yet complementary and to support the potential for one system to be engaged as a compensatory strategy when a counterpart system fails. Summary: Episodic memory, the ability to recall personal episodes, is the subtype of memory most often perceived as dysfunctional by patients and informants. Medial temporal lobe structures, especially the hippocampal formation and associated cortical and subcortical structures, are most often associated with episodic memory loss. Episodic memory dysfunction may present acutely, as in concussion; transiently, as in transient global amnesia (TGA); subacutely, as in thiamine deficiency; or chronically, as in Alzheimer disease. Semantic memory refers to acquired knowledge about the world. Anterior and inferior temporal lobe structures are most often associated with semantic memory loss. The semantic variant of primary progressive aphasia (svPPA) is the paradigmatic disorder resulting in predominant semantic memory dysfunction. Working memory, associated with frontal lobe function, is the active maintenance of information in the mind that can be potentially manipulated to complete goal-directed tasks. Procedural memory, the ability to learn skills that become automatic, involves the basal ganglia, cerebellum, and supplementary motor cortex. Parkinson disease and related disorders result in procedural memory deficits. Most memory concerns warrant bedside cognitive or neuropsychological evaluation and neuroimaging to assess for specific neuropathologies and guide treatment. PMID:26039844

  5. Concise Review: Mesenchymal Stem (Stromal) Cells: Biology and Preclinical Evidence for Therapeutic Potential for Organ Dysfunction Following Trauma or Sepsis.

    PubMed

    Matthay, Michael A; Pati, Shibani; Lee, Jae-Woo

    2017-02-01

    Several experimental studies have provided evidence that bone-marrow derived mesenchymal stem (stromal) cells (MSC) may be effective in treating critically ill surgical patients who develop traumatic brain injury, acute renal failure, or the acute respiratory distress syndrome. There is also preclinical evidence that MSC may be effective in treating sepsis-induced organ failure, including evidence that MSC have antimicrobial properties. This review considers preclinical studies with direct relevance to organ failure following trauma, sepsis or major infections that apply to critically ill patients. Progress has been made in understanding the mechanisms of benefit, including MSC release of paracrine factors, transfer of mitochondria, and elaboration of exosomes and microvesicles. Regardless of how well they are designed, preclinical studies have limitations in modeling the complexity of clinical syndromes, especially in patients who are critically ill. In order to facilitate translation of the preclinical studies of MSC to critically ill patients, there will need to be more standardization regarding MSC production with a focus on culture methods and cell characterization. Finally, well designed clinical trials will be needed in critically ill patient to assess safety and efficacy. Stem Cells 2017;35:316-324.

  6. N-Acetylaspartate, a marker of both cellular dysfunction and neuronal loss: its relevance to studies of acute brain injury.

    PubMed

    Demougeot, C; Garnier, P; Mossiat, C; Bertrand, N; Giroud, M; Beley, A; Marie, C

    2001-04-01

    To evaluate the contribution of cellular dysfunction and neuronal loss to brain N-acetylaspartate (NAA) depletion, NAA was measured in brain tissue by HPLC and UV detection in rats subjected to cerebral injury, associated or not with cell death. When lesion was induced by intracarotid injection of microspheres, the fall in NAA was related to the degree of embolization and to the severity of brain oedema. When striatal lesion was induced by local injection of malonate, the larger the lesion volume, the higher the NAA depletion. However, reduction of brain oedema and striatal lesion by treatment with the lipophilic iron chelator dipyridyl (20 mg/kg, 1 h before and every 8 h after embolization) and the inducible nitric oxide synthase inhibitor aminoguanidine (100 mg/kg given 1 h before malonate and then every 9 h), respectively, failed to ameliorate the fall in NAA. Moreover, after systemic administration of 3-nitropropionic acid, a marked reversible fall in NAA striatal content was observed despite the lack of tissue necrosis. Overall results show that cellular dysfunction can cause higher reductions in NAA level than neuronal loss, thus making of NAA quantification a potential tool for visualizing the penumbra area in stroke patients.

  7. Changes in Pain, Dysfunction, and Grip Strength of Patients with Acute Lateral Epicondylitis Caused by Frequency of Physical Therapy: A Randomized Controlled Trial

    PubMed Central

    Lee, Soyoung; Ko, Youngjun; Lee, Wanhee

    2014-01-01

    [Purpose] The purpose of this study was to investigate the changes in pain, dysfunction, and grip strength of patients with acute lateral epicondylitis and to suggest the appropriate treatment frequency and period. [Subjects] The subjects were divided into three: 2 days per week group (n=12), 3 days per week group (n=15), and 6 days per week group (n=13). [Methods] All groups received conventional physical therapy for 40 minutes and therapeutic exercises for 20 minutes per session during 6 weeks. The outcome measurements were the visual analogue scale (VAS), Patient-Rated Tennis Elbow Evaluation (PRTEE), and grip strength. [Results] The results of this study were as follows: at 3 weeks, there were no significant differences in VAS and PRTEE in the 3 groups, but at 6 weeks, 6 days per week group significantly decreased these two outcomes. Grip strength was significantly increased in 3 and 6 days per week groups at 6 weeks. [Conclusion] In conclusion, physical therapy is needed 3 days per week for 3 weeks in patients with acute lateral epicondylitis. After 3 weeks, 6 days per week is the most effective treatment frequency. PMID:25140091

  8. Effect of colporrhaphy on the Sexual Dysfunction of women with pelvic organ prolapsed

    PubMed Central

    Shahghaibi, Sholeh; Faizi, Sana; Gharibi, Fardin

    2013-01-01

    Objective: To evaluate the effect of colporrhaphy on sexual problems of women with pelvic organ prolapseis. Methodology: Sixty patients with pelvic organ prolapse (cystocele - rectocele) in a quasi-experimental study before and after treatment were included. Presence of pelvic organ prolapseis was assessed by examination in the lithotomy position. Degree of prolapse was determined according to Pelvic organ Prolapse Quantification (POPQ). Their degree of prolapse was marked from 1 to 3 then was colporrhaphy performed. Follow up of patients for sexual satisfaction was performed three and six months after surgery by telephone and interviews. Data were analyzed by SPSS version 15, the McNamara test, T-test, absolute and relative frequency, mean and standard deviation. Results: In sixty (60) women who were studied the mean and standard deviation of pregnancy and delivery rate were 4.4 ±2.2 and 4±2.1 respectively. About 65% of patients were over 35 years of age, 88.3% of women had the history of vaginal delivery and 10% of them had both the history of vaginal delivery and cesarean section. Score of sexual desire abstaining from sex and orgasm due to vaginal bulge before, 3 months and 6 months after colporrhaphy was significant (p=0.0001), but of sexual arousal scores there was no differences between each other. Mean of sexual satisfaction before operation was 30.75±5.70 and three months after operation it was 33.77±4.24 and six months after operation 36.03±3.5 which according to T-Test there was significant (p=0.0001). Conclusion: Sexual desire, orgasm and sexual satisfaction increased after colporrhaphy, frequency of intercourse and sexual arousal remains unchanged. It appears that colporrhaphy reduce symptoms associated with prolapse which is leading to sexual dissatisfaction and improved sexual satisfaction. PMID:24353530

  9. The Parenteral Vitamin C Improves Sepsis and Sepsis-Induced Multiple Organ Dysfunction Syndrome via Preventing Cellular Immunosuppression

    PubMed Central

    Chai, Yan-Fen

    2017-01-01

    Cellular immunosuppression appears to be involved in sepsis and sepsis-induced multiple organ dysfunction syndrome (MODS). Recent evidence showed that parenteral vitamin C (Vit C) had the ability to attenuate sepsis and sepsis-induced MODS. Herein, we investigated the impact of parenteral Vit C on cellular immunosuppression and the therapeutic value in sepsis. Using cecal ligation and puncture (CLP), sepsis was induced in WT and Gulo−/− mice followed with 200 mg/Kg parenteral Vit C administration. The immunologic functions of CD4+CD25+ regulatory T cells (Tregs) and CD4+CD25− T cells, as well as the organ functions, were determined. Administration of parenteral Vit C per se markedly improved the outcome of sepsis and sepsis-induced MODS of WT and Gulo−/− mice. The negative immunoregulation of Tregs was inhibited, mainly including inhibiting the expression of forkhead helix transcription factor- (Foxp-) 3, cytotoxic T lymphocyte associated antigen- (CTLA-) 4, membrane associated transforming growth factor-β (TGF-βm+), and the secretion of inhibitory cytokines [including TGF-β and interleukin- (IL-) 10], as well as CD4+ T cells-mediated cellular immunosuppression which was improved by parenteral Vit C in WT and Gulo−/− septic mice. These results suggested that parenteral Vit C has the ability to improve the outcome of sepsis and sepsis-induced MODS and is associated with improvement in cellular immunosuppression. PMID:28210072

  10. Ringer's malate solution protects against the multiple organ injury and dysfunction caused by hemorrhagic shock in rats.

    PubMed

    Dai, Zhong-Liang; Wu, Jing; Meng, Chen; Zeng, Fang; Yang, Yan; Yao, Shang-Long

    2012-08-01

    Malic acid, in the form of its anion malate, is a key intermediate in the major biochemical energy-producing cycle known as the citric acid or Krebs cycle. In this study, the authors investigated the protective effect of a novel crystalloid solution of Ringer's malate following fluid resuscitation of hemorrhagic shock using a rat model. Under general anesthesia, Sprague-Dawley male rats were subjected to 60 min of hemorrhagic shock (40 mmHg for 60 min) followed by crystalloid resuscitation. Groups were as follows: (1) sham shock, (2) normal saline, (3) Ringer's lactate, and (4) Ringer's malate. The experiment was terminated at 4 h after resuscitation. Mean arterial blood pressure (MAP) and blood biophysical parameters were monitored during the experiment. The alanine aminotransferase, aspartate aminotransferase, urea, creatinine, superoxide dismutase, and malondialdehyde levels in plasma were detected. The intestine, liver, lung, and renal histopathology were measured. It was found that Ringer's malate could increase MAP immediately and maintain MAP for a long time. Ringer's malate could reduce the level of alanine aminotransferase, aspartate aminotransferase, urea, and creatinine. At the same time, the activity of superoxide dismutase was increased, and the level of malondialdehyde was decreased. Histopathology indicated that Ringer's malate can protect against the multiple organ injury caused by hemorrhagic shock in rats. Ringer's malate prevented circulatory failure and alleviated multiple organ dysfunction syndrome in animals with hemorrhagic shock. The study suggests that Ringer's malate solution could be a potential novel therapeutic agent for fluid resuscitation.

  11. The Parenteral Vitamin C Improves Sepsis and Sepsis-Induced Multiple Organ Dysfunction Syndrome via Preventing Cellular Immunosuppression.

    PubMed

    Gao, Yu-Lei; Lu, Bin; Zhai, Jian-Hua; Liu, Yan-Cun; Qi, Hai-Xia; Yao, Ying; Chai, Yan-Fen; Shou, Song-Tao

    2017-01-01

    Cellular immunosuppression appears to be involved in sepsis and sepsis-induced multiple organ dysfunction syndrome (MODS). Recent evidence showed that parenteral vitamin C (Vit C) had the ability to attenuate sepsis and sepsis-induced MODS. Herein, we investigated the impact of parenteral Vit C on cellular immunosuppression and the therapeutic value in sepsis. Using cecal ligation and puncture (CLP), sepsis was induced in WT and Gulo(-/-) mice followed with 200 mg/Kg parenteral Vit C administration. The immunologic functions of CD4(+)CD25(+) regulatory T cells (Tregs) and CD4(+)CD25(-) T cells, as well as the organ functions, were determined. Administration of parenteral Vit C per se markedly improved the outcome of sepsis and sepsis-induced MODS of WT and Gulo(-/-) mice. The negative immunoregulation of Tregs was inhibited, mainly including inhibiting the expression of forkhead helix transcription factor- (Foxp-) 3, cytotoxic T lymphocyte associated antigen- (CTLA-) 4, membrane associated transforming growth factor-β (TGF-β(m+)), and the secretion of inhibitory cytokines [including TGF-β and interleukin- (IL-) 10], as well as CD4(+) T cells-mediated cellular immunosuppression which was improved by parenteral Vit C in WT and Gulo(-/-) septic mice. These results suggested that parenteral Vit C has the ability to improve the outcome of sepsis and sepsis-induced MODS and is associated with improvement in cellular immunosuppression.

  12. Elizabethkingia anophelis Isolated from Patients with Multiple Organ Dysfunction Syndrome and Lower Respiratory Tract Infection: Report of Two Cases and Literature Review.

    PubMed

    Hu, Shaohua; Jiang, Tao; Zhang, Xia; Zhou, Yajun; Yi, Zhengjun; Wang, Youxi; Zhao, Sishou; Wang, Mingxi; Ming, Desong; Chen, Shicheng

    2017-01-01

    Elizabethkingia anophelis, originally discovered from Anopheles mosquito gut, is an emerging pathogen, especially in immunocompromised patients. We isolated two strains of E. anophelis from two separate patients with multiple organ dysfunction syndrome and lower respiratory tract infection. In this paper, we reviewed the status of E. anophelis infection and its antibiotics resistance from reported cases.

  13. Elizabethkingia anophelis Isolated from Patients with Multiple Organ Dysfunction Syndrome and Lower Respiratory Tract Infection: Report of Two Cases and Literature Review

    PubMed Central

    Hu, Shaohua; Jiang, Tao; Zhang, Xia; Zhou, Yajun; Yi, Zhengjun; Wang, Youxi; Zhao, Sishou; Wang, Mingxi; Ming, Desong; Chen, Shicheng

    2017-01-01

    Elizabethkingia anophelis, originally discovered from Anopheles mosquito gut, is an emerging pathogen, especially in immunocompromised patients. We isolated two strains of E. anophelis from two separate patients with multiple organ dysfunction syndrome and lower respiratory tract infection. In this paper, we reviewed the status of E. anophelis infection and its antibiotics resistance from reported cases. PMID:28337189

  14. Nox2-dependent glutathionylation of endothelial NOS leads to uncoupled superoxide production and endothelial barrier dysfunction in acute lung injury.

    PubMed

    Wu, Feng; Szczepaniak, William S; Shiva, Sruti; Liu, Huanbo; Wang, Yinna; Wang, Ling; Wang, Ying; Kelley, Eric E; Chen, Alex F; Gladwin, Mark T; McVerry, Bryan J

    2014-12-15

    Microvascular barrier integrity is dependent on bioavailable nitric oxide (NO) produced locally by endothelial NO synthase (eNOS). Under conditions of limited substrate or cofactor availability or by enzymatic modification, eNOS may become uncoupled, producing superoxide in lieu of NO. This study was designed to investigate how eNOS-dependent superoxide production contributes to endothelial barrier dysfunction in inflammatory lung injury and its regulation. C57BL/6J mice were challenged with intratracheal LPS. Bronchoalveolar lavage fluid was analyzed for protein accumulation, and lung tissue homogenate was assayed for endothelial NOS content and function. Human lung microvascular endothelial cell (HLMVEC) monolayers were exposed to LPS in vitro, and barrier integrity and superoxide production were measured. Biopterin species were quantified, and coimmunoprecipitation (Co-IP) assays were performed to identify protein interactions with eNOS that putatively drive uncoupling. Mice exposed to LPS demonstrated eNOS-dependent increased alveolar permeability without evidence for altered canonical NO signaling. LPS-induced superoxide production and permeability in HLMVEC were inhibited by the NOS inhibitor nitro-l-arginine methyl ester, eNOS-targeted siRNA, the eNOS cofactor tetrahydrobiopterin, and superoxide dismutase. Co-IP indicated that LPS stimulated the association of eNOS with NADPH oxidase 2 (Nox2), which correlated with augmented eNOS S-glutathionylation both in vitro and in vivo. In vitro, Nox2-specific inhibition prevented LPS-induced eNOS modification and increases in both superoxide production and permeability. These data indicate that eNOS uncoupling contributes to superoxide production and barrier dysfunction in the lung microvasculature after exposure to LPS. Furthermore, the results implicate Nox2-mediated eNOS-S-glutathionylation as a mechanism underlying LPS-induced eNOS uncoupling in the lung microvasculature.

  15. Acute Renal Failure after Consumption of Fish Gall Bladder

    PubMed Central

    Yu Yao, Bian

    2014-01-01

    A case of acute renal failure after consumption of fish gall bladder as traditional medical remedy is reported. The patient fully recovered with conservative treatment. The risk of acute kidney failure and even multiple organ dysfunction syndrome following ingestion of fish gall bladder is highlighted. PMID:24829840

  16. Acute pancreatitis as a model of SIRS.

    PubMed

    Bhatia, Madhav

    2009-01-01

    Acute pancreatitis is a common clinical condition. Excessive systemic inflammatory response syndrome (SIRS) in acute pancreatitis leads to distant organ damage and multiple organ dysfunction syndrome (MODS), which is the primary cause of morbidity and mortality in this condition. Development of in vivo experimental models of acute pancreatitis and associated systemic organ damage has enabled us to study the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and associated systemic organ damage. Using these models, recent studies by us and other investigators have established the critical role played by inflammatory mediators such as TNF-a, IL-1b, IL-6, PAF, IL-10, CD40L, C5a, ICAM-1, chemokines, substance P and hydrogen sulfide in acute pancreatitis and the resultant MODS. This chapter intends to present an overview of different experimental animal models of acute pancreatitis and associated MODS and the role of inflammatory mediators in the pathogenesis of this condition.

  17. T cell abundance in blood predicts acute organ toxicity in chemoradiotherapy for head and neck cancer

    PubMed Central

    Reichardt, Sybille D.; Rave-Fränk, Margret; Schirmer, Markus A.; Stadelmann, Christine; Canis, Martin; Wolff, Hendrik A.

    2016-01-01

    Treatment of head and neck squamous cell carcinoma (HNSCC) by chemoradiotherapy (CRT) often results in high-grade acute organ toxicity (HGAOT). As these adverse effects impair the patients' quality of life and the feasibility of the planned therapy, we sought to analyze immunological parameters in tumor material and blood samples obtained from 48 HNSCC patients in order to assess the potential to predict the individual acute organ toxicity. T cells in the tumor stroma were enriched in patients developing HGAOT whereas levels of soluble factors in the plasma and gene expression in whole blood did not coincide with the occurrence of acute organ toxicity. In contrast, the frequency and absolute numbers of selected leukocyte subpopulations measured in samples of peripheral blood mononuclear cells (PBMCs) directly before the beginning of CRT were significantly different in patients with HGAOT as compared to those without. When we validated several potential markers including the abundance of T cells in a small prospective study with 16 HNSCC patients, we were able to correctly predict acute organ toxicity in up to 81% of the patients. We conclude that analysis of PBMCs by fluorescence-activated cell sorting (FACS) might be a convenient strategy to identify patients at risk of developing HGAOT caused by CRT, which might allow to adapt the treatment regimen and possibly improve disease outcome. PMID:27589568

  18. EVALUATION OF MINIMUM DATA REQUIREMENTS FOR ACUTE TOXICITY VALUE EXTRAPOLATION WITH AQUATIC ORGANISMS

    EPA Science Inventory

    Buckler, Denny R., Foster L. Mayer, Mark R. Ellersieck and Amha Asfaw. 2003. Evaluation of Minimum Data Requirements for Acute Toxicity Value Extrapolation with Aquatic Organisms. EPA/600/R-03/104. U.S. Environmental Protection Agency, National Health and Environmental Effects Re...

  19. Organization of Care for Acute Myocardial Infarction in Rural and Urban Hospitals in Kansas

    ERIC Educational Resources Information Center

    Ellerbeck, Edward F.; Bhimaraj, Arvind; Perpich, Denise

    2004-01-01

    One in 4 Americans lives in a rural community and relies on rural hospitals and medical systems for emergent care of acute myocardial infarctions (AMI). The infrastructure and organization of AMI care in rural and urban Kansas hospitals was examined. Using a nominal group process, key elements within hospitals that might influence quality of AMI…

  20. [Micro-organism translocation and acute anastomosis inflammation after stomach resection].

    PubMed

    Gulov, M K; Kurbonov, K M

    2003-10-01

    The results of examination of 42 patients with an acute anastomositis after performance of gastric resection were analyzed. Clinical classification was elaborated for detailed interpretation of the anastomosits diagnosis and choice of therapy. Close correlative inter-relatioship between severity of anastomositis and degree of gastric mucosa colonization by micro-organisms was established basing on analysis of the laboratory and bacteriological investigations results.

  1. Resveratrol ameliorates oxidative stress and organ dysfunction in Schistosoma mansoni infected mice.

    PubMed

    Soliman, R H; Ismail, O A; Badr, M S; Nasr, S M

    2017-03-01

    Schistosoma mansoni causes a major chronic debilitating disease in more than 230 million people around the world. The pathognomonic granuloma is a major cause of the oxidative stress encountered as a consequence of infection not only in the liver, but also in other important organs as spleen, lung, brain and kidney. Resveratrol administration at a dose of 20 mg/kg once daily for two weeks to mice infected with Schistosoma mansoni resulted in improvement in serum cholesterol and triglyceride levels. Enzymatic antioxidant profile showed significant modulations in Superoxide dismutase, catalase activities and reduced glutathione levels. Specific biomarkers for homeostasis of brain and lung i.e. Tau and RAGE respectively, showed significant improvement after resveratrol administration.

  2. Serial measurement of NT-proBNP predicts adverse cardiovascular outcome in children with primary myocardial dysfunction and acute decompensated heart failure (ADHF)

    PubMed Central

    Medar, Shivanand; Hsu, Daphne T.; Ushay, H. Michael; Lamour, Jacqueline M.; Cohen, Hillel W; Killinger, James S.

    2015-01-01

    Introduction In children, elevated amino terminal pro B-type naturetic peptide (NT-proBNP) levels are associated with impaired heart function. The predictive value of serial monitoring of NT-proBNP levels in acute decompensated heart failure (ADHF) is unclear. Methods This prospective observational study enrolled patients ≤ 21 years with primary myocardial dysfunction and ADHF. NT-proBNP levels were obtained on enrollment (D0), day 2 (D2) and day 7 (D7). Clinical, laboratory and imaging data were collected on enrollment. CV outcome was defined as Heart Transplant (HTx), Ventricular Assist Device (VAD) placement, Extracorporeal Membrane Oxygenation or death at 1 year after admission. NT-proBNP levels and the percent change from D0 to D2 and D0 to D7 were calculated and compared between those with and without adverse cardiovascular (ACV) outcome. Results Sixteen consecutive patients were enrolled. ACV outcome occurred in 6 (37.5%, 4 HTx and 2 VAD). In patients with an ACV outcome, median NT-ProBNP levels at D7 were significantly higher (7,365 Vs. 1,196 pg/ml; p= 0.02) and the percent decline in NT-proBNP was significantly smaller (28% vs. 73%, p=0.02) compared to those without an ACV outcome. ROC curve analysis revealed that a less than 55% decline in NT-proBNP levels at D7 had a sensitivity and specificity of 83% and 90% respectively in predicting an ACV [AUC 0.86, CI (0.68,1.0), p=0.02]. Conclusions In conclusion, children with primary myocardial dysfunction and ADHF, a persistently elevated NT-proBNP and/or a lesser degree of decline in NT-proBNP during the first week of presentation were strongly associated with ACV outcome. Serial NT-proBNP monitoring may allow the early identification of children at risk for worse outcome. PMID:25856472

  3. Renal Dysfunction Is an Independent Risk Factor for Poor Outcome in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis: A New Cutoff Value

    PubMed Central

    Farhoudi, Mehdi; Taheraghdam, Aliakbar; Savadi Oskouei, Daryoush; Yazdchi, Mohammad; Özdemir, Atilla Özcan

    2017-01-01

    Objective. This study was set to assess the effect of renal dysfunction on outcome of stroke patients treated with intravenous thrombolysis (IVT). Methods. This multicenter research involved 403 patients from January 2009 to March 2015. Patients were divided into two groups: (1) control group with GFR ≥ 45 mL/min/1.73 m2 and (2) low GFR group with GFR < 45 mL/min/1.73 m2. Outcome measurements were poor outcome (mRS 3–6) and mortality at 3 months and symptomatic intracerebral hemorrhage (SICH) within the first 24–36 hours. Univariate and multivariate regression analyses were performed, and odds ratios (ORs) were determined at 95% confidence intervals (CIs). Results. Univariate analyses determined that every decrease of GFR by 10 mL/min/1.73 m2 significantly increased the risk of poor outcome (OR 1.19, 95% CI 1.09–1.30, p < 0.001) and mortality (OR 1.18, 95% CI 1.06–1.32, p = 0.002). In multivariate regression, adjusted for all variables with p value < 0.1, low GFR (GFR < 45 versus GFR equal to or more than 45) was associated with poor outcome (OR adjusted 2.15, 95% CI 1.01–4.56, p = 0.045). Conclusion. In IVT for acute stroke, renal dysfunction with GFR < 45 mL/min/1.73 m2 before treatment determined increased odds for poor outcome compared to GFR of more than 45 mL/min/1.73 m2. PMID:28127492

  4. Renal Dysfunction Is an Independent Risk Factor for Poor Outcome in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis: A New Cutoff Value.

    PubMed

    Sadeghi-Hokmabadi, Elyar; Baş, Demet Funda; Farhoudi, Mehdi; Taheraghdam, Aliakbar; Savadi Oskouei, Daryoush; Yazdchi, Mohammad; Hashemilar, Maziyar; Uzuner, Nevzat; Mirnour, Reshad; Colak, Ertugrul; Özdemir, Atilla Özcan

    2017-01-01

    Objective. This study was set to assess the effect of renal dysfunction on outcome of stroke patients treated with intravenous thrombolysis (IVT). Methods. This multicenter research involved 403 patients from January 2009 to March 2015. Patients were divided into two groups: (1) control group with GFR ≥ 45 mL/min/1.73 m(2) and (2) low GFR group with GFR < 45 mL/min/1.73 m(2). Outcome measurements were poor outcome (mRS 3-6) and mortality at 3 months and symptomatic intracerebral hemorrhage (SICH) within the first 24-36 hours. Univariate and multivariate regression analyses were performed, and odds ratios (ORs) were determined at 95% confidence intervals (CIs). Results. Univariate analyses determined that every decrease of GFR by 10 mL/min/1.73 m(2) significantly increased the risk of poor outcome (OR 1.19, 95% CI 1.09-1.30, p < 0.001) and mortality (OR 1.18, 95% CI 1.06-1.32, p = 0.002). In multivariate regression, adjusted for all variables with p value < 0.1, low GFR (GFR < 45 versus GFR equal to or more than 45) was associated with poor outcome (OR adjusted 2.15, 95% CI 1.01-4.56, p = 0.045). Conclusion. In IVT for acute stroke, renal dysfunction with GFR < 45 mL/min/1.73 m(2) before treatment determined increased odds for poor outcome compared to GFR of more than 45 mL/min/1.73 m(2).

  5. Differentially expressed miRNAs in sepsis-induced acute kidney injury target oxidative stress and mitochondrial dysfunction pathways

    PubMed Central

    Ge, Qin-Min; Huang, Chun-Mei; Zhu, Xiang-Yang; Bian, Fan; Pan, Shu-Ming

    2017-01-01

    Objective To identify specific miRNAs involved in sepsis-induced AKI and to explore their targeting pathways. Methods The expression profiles of miRNAs in serum from patients with sepsis-induced AKI (n = 6), sepsis-non AKI (n = 6), and healthy volunteers (n = 3) were investigated by microarray assay and validated by quantitative PCR (qPCR). The targets of the differentially expressed miRNAs were predicted by Target Scan, mirbase and Miranda. Then the significant functions and involvement in signaling pathways of gene ontology (GO) and KEGG pathways were analyzed. Furthermore, eight miRNAs were randomly selected out of the differentially expressed miRNAs for further testing by qPCR. Results qPCR analysis confirmed that the expressions levels of hsa-miR-23a-3p, hsa-miR-4456, hsa-miR-142-5p, hsa-miR-22-3p and hsa-miR-191-5p were significantly lower in patients with sepsis compared with the healthy volunteers, while hsa-miR-4270, hsa-miR-4321, hsa-miR-3165 were higher in the sepsis patients. Statistically, miR-4321; miR-4270 were significantly upregulated in the sepsis-induced AKI compared with sepsis-non AKI, while only miR-4321 significantly overexpressed in the sepsis groups compared with control groups. GO analysis showed that biological processes regulated by the predicted target genes included diverse terms. They were related to kidney development, regulation of nitrogen compound metabolic process, regulation of cellular metabolic process, cellular response to oxidative stress, mitochondrial outer membrane permeabilization, etc. Pathway analysis showed that several significant pathways of the predicted target genes related to oxidative stress. miR-4321 was involved in regulating AKT1, mTOR and NOX5 expression while miR-4270 was involved in regulating PPARGC1A, AKT3, NOX5, PIK3C3, WNT1 expression. Function and pathway analysis highlighted the possible involvement of miRNA-deregulated mRNAs in oxidative stress and mitochondrial dysfunction. Conclusion This study

  6. Long-term follow-up for organic dysfunction in breech – presenting children

    PubMed Central

    Preis, Krzysztof; Bidzan, Mariola; Swiatkowska-Freund, Małgorzata; Peplińska, Aleksandra

    2012-01-01

    Summary Background The authors performed a long term outcome analysis of minimal brain damage in children delivered in breech presentation, and related the results to the mode of delivery (vaginal or by cesarean section). Material/Methods In the Department of Obstetrics at the Medical University of Gdansk (Poland), 917 breech deliveries took place between 1981 and 1990. Excluding stillbirths and multiple pregnancies, 874 deliveries were analyzed. We received positive responses from 232 mothers, who provided us with considerable information about the children’s further development and problems that had arisen during their school years. All the respondents were contacted by telephone, and 83 of them agreed to visit our Department with their children to undergo a psychological examination – the following tests were performed: 1) the Bender-Kopitz Test (BKT), and 2) the Benton Visual Retention Test (BVRT). Results The mode of delivery for all groups and subgroups had no influence on the incidence of organic brain disorders in later childhood, assessed by the Benton Visual Retention test and by the Bender-Kopitz test. Conclusions Vaginal breech deliveries are safe in both primiparous and multiparous mothers. PMID:23197237

  7. Acute Exposure to Low Glucose Rapidly Induces Endothelial Dysfunction and Mitochondrial Oxidative Stress: Role for AMP Kinase

    PubMed Central

    Wang, Jingli; Alexanian, Anna; Ying, Rong; Kizhakekuttu, Tinoy J.; Dharmashankar, Kodlipet; Vasquez-Vivar, Jeanette; Gutterman, David D.; Widlansky, Michael E.

    2012-01-01

    Objective Hypoglycemia is associated with increased mortality. The reasons for this remain unclear and the effects of low glucose exposure on vascular endothelial function remain largely unknown. We endeavored to determine the effects of low glucose on endothelial cells and intact human arterioles. Methods and Results We exposed human umbilical vein endothelial cells to low glucose conditions in a clinically relevant range (40–70 mg/dL) and found rapid and marked reductions in nitric oxide (NO) bioavailability (P<0.001). This was associated with concomitantly increased mitochondrial superoxide production (P<0.001) and NO-dependent mitochondrial hyperpolarization (P<0.001). Reduced NO bioavailability was rapid and attributable to reduced eNOS activity and destruction of NO. Low glucose rapidly activated AMP Kinase but physiological activation failed to restore NO bioavailability. Pharmacological AMP Kinase activation led to phosphorylation of eNOS’s Ser633 activation site, reversing the adverse effects of low glucose, and this protective effect was prevented by L-NAME. Intact human arterioles exposed to low glucose demonstrated marked endothelial dysfunction which was prevented by either metformin or TEMPOL. Conclusions Our data suggest that moderate low glucose exposure rapidly impairs NO bioavailability and endothelial function in the human endothelium, and that pharmacological AMP Kinase activation can inhibit this effect in an NO-dependent manner. PMID:22207730

  8. Acute abdomen caused by bladder rupture attributable to neurogenic bladder dysfunction following a stroke: a case report

    PubMed Central

    2011-01-01

    Introduction Spontaneous bladder rupture is a rare and serious event with high mortality. It is not often considered in the patient presenting with peritonitis. This often leads to delays in diagnosis. There are very few case reports of true spontaneous rupture in the literature. This is the first such reported case in which bladder rupture was attributable to neurogenic bladder dysfunction following a stroke. Case presentation We report the case of a 67-year-old Caucasian man who presented with lower abdominal pain and a peritonitic abdomen. He had a long-term urethral catheter because of urinary retention following a previous stroke. He was treated conservatively with antibiotics before a surgical opinion was sought. Exploratory laparotomy confirmed the diagnosis of spontaneous bladder rupture. After repair of the defect, he eventually made a full recovery. Conclusion In this unusual case report, we describe an example of a serious event in which delays in diagnosis may lead to increased morbidity and mortality. To date, no unifying theory explaining why rupture occurs has been postulated. We conducted a thorough literature search to examine the etiological factors in other published cases. These etiological factors either increase intra-vesical pressure or decrease the strength of the bladder wall. We hope that by increasing awareness of these etiological factors, spontaneous bladder rupture may be diagnosed earlier and appropriate therapy started. PMID:21714888

  9. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature.

    PubMed

    Kleinschnitz, Christoph; Kraft, Peter; Dreykluft, Angela; Hagedorn, Ina; Göbel, Kerstin; Schuhmann, Michael K; Langhauser, Friederike; Helluy, Xavier; Schwarz, Tobias; Bittner, Stefan; Mayer, Christian T; Brede, Marc; Varallyay, Csanad; Pham, Mirko; Bendszus, Martin; Jakob, Peter; Magnus, Tim; Meuth, Sven G; Iwakura, Yoichiro; Zernecke, Alma; Sparwasser, Tim; Nieswandt, Bernhard; Stoll, Guido; Wiendl, Heinz

    2013-01-24

    We have recently identified T cells as important mediators of ischemic brain damage, but the contribution of the different T-cell subsets is unclear. Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) are generally regarded as prototypic anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. In the present study, we examined the role of Tregs after experimental brain ischemia/reperfusion injury. Selective depletion of Tregs in the DEREG mouse model dramatically reduced infarct size and improved neurologic function 24 hours after stroke and this protective effect was preserved at later stages of infarct development. The specificity of this detrimental Treg effect was confirmed by adoptive transfer experiments in wild-type mice and in Rag1(-/-) mice lacking lymphocytes. Mechanistically, Tregs induced microvascular dysfunction in vivo by increased interaction with the ischemic brain endothelium via the LFA-1/ICAM-1 pathway and platelets and these findings were confirmed in vitro. Ablation of Tregs reduced microvascular thrombus formation and improved cerebral reperfusion on stroke, as revealed by ultra-high-field magnetic resonance imaging at 17.6 Tesla. In contrast, established immunoregulatory characteristics of Tregs had no functional relevance. We define herein a novel and unexpected role of Tregs in a primary nonimmunologic disease state.

  10. Long-term bioavailability of redox nanoparticles effectively reduces organ dysfunctions and death in whole-body irradiated mice.

    PubMed

    Feliciano, Chitho P; Tsuboi, Koji; Suzuki, Kenshi; Kimura, Hiroyuki; Nagasaki, Yukio

    2017-06-01

    Radioprotective agents have been developed to protect patients against the damaging and lethal effects of ionizing radiation. However, in addition to the intrinsic ability to target reactive oxygen species (ROS), the ability to retain a significant level of bioavailability is desirable in radioprotective agents because that would increase and prolong their radioprotective efficacy and improve its safety. Here, we report the development of a novel nanoparticle-based radioprotective agent with improved bioavailability, which suppressed the adverse effects typically associated with low-molecular-weight (LMW) antioxidants. We developed biocompatible and colloidally stable nanoparticles in which nitroxide radicals that were covalently conjugated (redox nanoparticles, RNP(N)) effectively scavenged radiation-induced ROS with a characteristically prolonged bioavailability and tissue-residence time compared with that of conventional LMW antioxidants. The confinement of the nitroxide radicals in the RNP(N) core prevented its rapid metabolism and excretion out of the body. The nano-sized formulation prevented internalization of RNP(N) in healthy cells, thereby preserving the normal function of the redox reactions in the cell. This improved pharmacological performance dramatically reduced the radiation-induced organ dysfunctions and increased the survival time of the lethally irradiated mice when the nanoparticles were administered 3-24 h before whole-body irradiation.

  11. Pathogenesis of multiple organ dysfunction syndrome--endotoxin, inflammatory cells, and their mediators: cytokines and reactive oxygen species.

    PubMed

    Maier, R V

    2000-01-01

    Multiple organ dysfunction syndrome (MODS) is caused by an overwhelming, uncontrolled systemic inflammatory response that is activated by a number of hostile stimuli including sepsis, hypovolemic shock, and severe trauma resulting in massive tissue injury. The indiscriminate activation of the inflammatory response due to these insults causes loss of the host's ability to localize the inflammation to the focus of the problem, leading to systemic inflammation and severe host tissue damage and subsequent MODS. While the major players, namely neutrophils, macrophages, endotoxin, cytokines, and oxidants have been known for some time, the disease processes responsible for the pathogenesis of MODS have only recently been elucidated. Our newly found knowledge has resulted in the development of novel therapeutic strategies to prevent or treat MODS, such as scavenging toxic oxygen species and inhibiting endotoxin, or cytokine production, or cytokine activity. Unfortunately, these strategies have not resulted in improved mortality rates among patients with MODS. The complex nature of the host response to severe insults combined with the fact that the host has multiple, redundant parallel systems to deal with various insults has made it difficult for clinical interventions to adequately ameliorate the disease process among patients at risk for MODS. The purpose of this article is to attempt to "dissect out" several individual components of the inflammatory response that play important roles in the development of MODS and to review some potentially beneficial approaches to combat these harmful processes.

  12. [Organ-protection therapy. A new therapeutic approach for acute heart failure?].

    PubMed

    Chivite, David; Formiga, Francesc; Corbella, Xavier

    2014-03-01

    Unlike the prolonged benefit produced by the treatment of chronic heart failure, newer drugs tested for the treatment of acute heart failure in the last decade have failed to provide evidence of clinical benefit beyond some improvement in symptom relief. In particular, no drug has shown the ability to reduce the higher medium- and long-term risk of morbidity and mortality in these patients after an episode of decompensation. Current understanding of the pathophysiology of acute heart failure and its consequences has led to the hypothesis that, beyond symptom control, effective therapies for this syndrome should target not only the hemodynamic changes of the initial phase of the syndrome but should also "protect" the organism from the activation of neurohumoral and inflammatory pathways triggered by the decompensation episode, which persist in time and confer a risk of deleterious effects in several organs and tissues. Serelaxin, a new drug related to the peptidic endogenous hormones of the relaxin family, has recently been shown to provide multiple beneficial effects in terms of "organ protection" - not only in the cardiovascular and renal systems - from these acute heart failure-related deleterious changes. This drug has already been tested in acute heart failure patients with encouraging results in terms of medium-term clinical benefit, rendering serelaxin as a serious candidate for first-line, prognosis-modifying therapy in this syndrome.

  13. Pattern of cytokine (IL-6 and IL-10) level as inflammation and anti-inflammation mediator of multiple organ dysfunction syndrome (MODS) in polytrauma.

    PubMed

    Sapan, Heber Bombang; Paturusi, Idrus; Jusuf, Irawan; Patellongi, Ilhamjaya; Massi, Muh Nasrum; Pusponegoro, Aryono Djuned; Arief, Syafrie Kamsul; Labeda, Ibrahim; Islam, Andi Asadul; Rendy, Leo; Hatta, Mochammad

    2016-01-01

    Massive injury remains the most common cause of death for productive age group globally. The current immune, inflammatory paradigm, based on an incomplete understanding of the functional integration of the complex host response, remains a major impediment to the development of effective innovative diagnostic and therapeutic effort. This study attempt to investigate the pattern of inflammatory and anti-inflammatory cytokines such as interleukin-6 and 10 (IL-6 and IL-10) and their interaction in severe injury condition with its major complication as multiple organ dysfunction syndrome (MODS) and failure (MOF) after polytrauma. This is multicenter study held at 4 academic Level-1 Trauma center included 54 polytrauma participants. Inclusion criteria were age between 16-60 years old, had new acute episode of polytrauma which defined as injury in ≥2 body region with Injury Severity Score (ISS) ≥16, and the presence of Systemic Inflammation Response Syndrome (SIRS). Serum level of IL-6 and IL-10 were taken on day 2, 3, and 5 after trauma. During hospitalization, samples were observed for the occurrence of MODS or MOF using Sequential Organ Failure Assessment (SOFA) and mortality rate were also noted. Participant were mostly male with mean of age of 35, 9 years old, endured polytrauma caused by traffic accident. Elevation of cytokines (IL-6, IL-10, and IL-6/IL-10 ratio) had directly proportional with MODS and mortality. Threshold level of compensation for severe trauma is IL-6 of 50 pg/mL and trauma load of ISS ≥30. Inflammation reaction greater than this threshold level would result in downhill level of IL-6, IL-10, or IL-6/IL-10 ratio which associated with poor outcome (MODS and death). The elevation of these cytokines level were represent as compensation/adaptive immune system and its fall represent decompensating/failure of immune system after severe trauma. The pattern of IL-6 and IL-10 after polytrauma represent immune system effort to restore homeostasis

  14. Pattern of cytokine (IL-6 and IL-10) level as inflammation and anti-inflammation mediator of multiple organ dysfunction syndrome (MODS) in polytrauma

    PubMed Central

    Sapan, Heber Bombang; Paturusi, Idrus; Jusuf, Irawan; Patellongi, Ilhamjaya; Massi, Muh Nasrum; Pusponegoro, Aryono Djuned; Arief, Syafrie Kamsul; Labeda, Ibrahim; Islam, Andi Asadul; Rendy, Leo; Hatta, Mochammad

    2016-01-01

    Massive injury remains the most common cause of death for productive age group globally. The current immune, inflammatory paradigm, based on an incomplete understanding of the functional integration of the complex host response, remains a major impediment to the development of effective innovative diagnostic and therapeutic effort. This study attempt to investigate the pattern of inflammatory and anti-inflammatory cytokines such as interleukin-6 and 10 (IL-6 and IL-10) and their interaction in severe injury condition with its major complication as multiple organ dysfunction syndrome (MODS) and failure (MOF) after polytrauma. This is multicenter study held at 4 academic Level-1 Trauma center included 54 polytrauma participants. Inclusion criteria were age between 16-60 years old, had new acute episode of polytrauma which defined as injury in ≥2 body region with Injury Severity Score (ISS) ≥16, and the presence of Systemic Inflammation Response Syndrome (SIRS). Serum level of IL-6 and IL-10 were taken on day 2, 3, and 5 after trauma. During hospitalization, samples were observed for the occurrence of MODS or MOF using Sequential Organ Failure Assessment (SOFA) and mortality rate were also noted. Participant were mostly male with mean of age of 35, 9 years old, endured polytrauma caused by traffic accident. Elevation of cytokines (IL-6, IL-10, and IL-6/IL-10 ratio) had directly proportional with MODS and mortality. Threshold level of compensation for severe trauma is IL-6 of 50 pg/mL and trauma load of ISS ≥30. Inflammation reaction greater than this threshold level would result in downhill level of IL-6, IL-10, or IL-6/IL-10 ratio which associated with poor outcome (MODS and death). The elevation of these cytokines level were represent as compensation/adaptive immune system and its fall represent decompensating/failure of immune system after severe trauma. The pattern of IL-6 and IL-10 after polytrauma represent immune system effort to restore homeostasis

  15. Testosterone deficiency causes penile fibrosis and organic erectile dysfunction in aging men. Evaluating association among Age, TDS and ED

    PubMed Central

    2012-01-01

    Introduction We studied the possible correlation between age, testosterone deficiency, cavernosal fibrosis and erectile dysfunction (ED). Methods 47 patients with ED were enrolled between September 2010 and October 2011. IIEF-EF score, NPTR test using the Rigiscan method, total and free testosterone levels, and cavernosum biopsy were carried out on all patients. Patients aged 65 or over were defined as Old Age (OA) while patients under 65 were defined Young age (YA). The strength of the relationships found was estimated by Odds Ratio. Results 74% of patients with values of over 52% collagen fibers in the corpora cavernosa were found to have organic ED. A significant difference was found in age, percentage of collagen fibers, testosterone levels between patients with Positive Rigiscan (PR) and Negative Rigiscan (NR). Hypotestosteronaemia increased the risk of ED with PR (OR: 21.4, 95% CI: 20.2-22.6) and in both young age patients (OR: 4.3, 95% CI: 2.4-6.2) and old age patients (OR: 15.5, 95% CI: 13.4-17.6). Moreover cavernosal fibrosis increased the risk of ED with PR in both young age patients (OR: 8.2, 95% CI: 6.4-10.0 and old age patients (OR: 24.6, 95% CI: 20.8-28.4). Conclusions This study demonstrates a strong association among age, testosterone deficiency, cavernosal fibrosis and ED with PR. Age, testosterone deficiency and cavernosal fibrosis are potentially correctable factors of cavernosal fibrosis and organic ED. Further, prospective studies are needed to evaluate if testosterone treatment, alone or in association with PDE5 inhibitors, may lower the risk of cavernosal fibrosis or decrease the severity the fibrosis in ED patients. PMID:23173727

  16. Bioconcentration and acute toxicity of polycyclic musks in two benthic organisms (Chironomus riparius and Lumbriculus variegatus).

    PubMed

    Artola-Garicano, Elsa; Sinnige, Theo L; van Holsteijn, Ineke; Vaes, Wouter H J; Hermens, Joop L M

    2003-05-01

    In the current study, the bioconcentration behavior and acute toxicity of two polycyclic musks, Tonalide 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN) and Galaxolide 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexa-methylcyclopenta[gamma]-2-benzopyran (HHCB), were studied in two benthic organisms. Polycyclic musks are frequently used fragrances, and they have been detected in different compartments of the environment. The aim of this study was to fill some empirical data gaps for AHTN and HHCB for benthic organisms. Results show that differences exist between both organisms. Chironomus riparius exhibited bioconcentration factors (BCFs) for AHTN and HHCB substantially lower than predicted for nontransformed organics. The BCFs for both chemicals increased after coexposure of the organism to the cytochrome P450 inhibitor piperonyl butoxide. Thus, the low BCF values were the result of rapid biotransformation of AHTN and HHCB in the midge larvae. Bioconcentration kinetics indicated that both chemicals induced their own cytochrome P450-mediated metabolism. Acute toxicity of AHTN to midge larvae was reduced compared to predicted baseline toxicity and was similar for HHCB. Bioconcentration of AHTN and HHCB in the worm (Lumbriculus variegatus) is in agreement with predictions based on the octanol-water partition coefficients of these chemicals. Acute toxicity was found to be similar to predicted values for baseline toxicity. Summarizing, for AHTN and HHCB, acute toxicity and bioconcentration behavior in L. variegatus was in accordance with predicted data for nontransformed organics. In C. riparius, bioconcentration as well as toxicity were reduced.

  17. [The particularities of acute surgical diseases treatment of abdominal cavity organs in patients with haemophilia].

    PubMed

    Shutov, S A; Karagiulia, S R; Danishian, K I; Zorenko, V Iu; Grzhimolovskiĭ, A V; Polianskaia, T Iu; Shulutko, E M; Galstian, G M

    2014-01-01

    The experience of treatment of 366 patients with haemophilia who were urgently hospitalized in hеmatological Scientific Center over the last 10 years is presented in the article. There were 114 (31.1%) patients with acute diseases of abdominal cavity organs, 150 (41%) patients with bleeding from upper gastrointestinal tract, 102 (27.9%) patients with acute hematomas of retroperitoneal space. Urgent operations were performed in 48 (22.2%) patients who were hospitalized with clinical symptoms of acute abdomen syndrome. It was developed the criteria of diagnosis and choice of treatment tactic on the basis of the received results. Application of presented algorithms led to improve the quality of urgent surgical care to patients with haemophilia.

  18. PLGA‐PNIPAM Microspheres Loaded with the Gastrointestinal Nutrient NaB Ameliorate Cardiac Dysfunction by Activating Sirt3 in Acute Myocardial Infarction

    PubMed Central

    Cheng, Panke; Zeng, Wen; Li, Li; Huo, Da; Zeng, Lingqing; Tan, Ju; Zhou, Jingting; Sun, Jiansen; Liu, Ge; Li, Yanzhao; Guan, Ge; Wang, Yuxin

    2016-01-01

    Acute myocardial infarction (AMI) is the death of cardiomyocytes caused by a lack of energy due to ischemia. Nutrients supplied by the blood are the main source of cellular energy for cardiomyocytes. Sodium butyrate (NaB), a gastrointestinal nutrient, is a short‐chain fatty acid (butyric acid) that may act as an energy source in AMI therapy. Poly(lactic‐co‐glycolic acid)‐Poly (N‐isopropylacrylamide) microspheres loaded with NaB (PP‐N) are synthesized to prolong the release of NaB and are injected into ischemic zones in a Sprague–Dawley rat AMI model. Here, this study shows that PP‐N can significantly ameliorate cardiac dysfunction in AMI, and NaB can specially bind to Sirt3 structure, activating its deacetylation ability and inhibiting the generation of reactive oxygen species, autophagy, and angiogenesis promotion. The results indicate that NaB, acting as a nutrient, can protect cardiomyocytes in AMI. These results suggest that the gastrointestinal nutrient NaB may be a new therapy for AMI treatment, and PP‐N may be the ideal therapeutic regimen. PMID:27981013

  19. Warm preconditioning protects against acute heat-induced respiratory dysfunction and delays bleaching in a symbiotic sea anemone.

    PubMed

    Hawkins, Thomas D; Warner, Mark E

    2017-03-15

    Preconditioning to non-stressful warming can protect some symbiotic cnidarians against the high temperature-induced collapse of their mutualistic endosymbiosis with photosynthetic dinoflagellates (Symbiodinium spp.), a process known as bleaching. Here, we sought to determine whether such preconditioning is underpinned by differential regulation of aerobic respiration. We quantified in vivo metabolism and mitochondrial respiratory enzyme activity in the naturally symbiotic sea anemone Exaiptasia pallida preconditioned to 30°C for >7 weeks as well as anemones kept at 26°C. Preconditioning resulted in increased Symbiodinium photosynthetic activity and holobiont (host+symbiont) respiration rates. Biomass-normalised activities of host respiratory enzymes [citrate synthase and the mitochondrial electron transport chain (mETC) complexes I and IV] were higher in preconditioned animals, suggesting that increased holobiont respiration may have been due to host mitochondrial biogenesis and/or enlargement. Subsequent acute heating of preconditioned and 'thermally naive' animals to 33°C induced dramatic increases in host mETC complex I and Symbiodinium mETC complex II activities only in thermally naive E. pallida These changes were not reflected in the activities of other respiratory enzymes. Furthermore, bleaching in preconditioned E. pallida (defined as the significant loss of symbionts) was delayed by several days relative to the thermally naive group. These findings suggest that changes to mitochondrial biogenesis and/or function in symbiotic cnidarians during warm preconditioning might play a protective role during periods of exposure to stressful heating.

  20. Acute and chronic toxicity of boron to a variety of freshwater organisms.

    PubMed

    Soucek, David J; Dickinson, Amy; Koch, Brian T

    2011-08-01

    Boron enters the aquatic environment from various sources, including weathering of borates, sewage effluents, coal combustion, use of cleaning compounds, and agrochemicals. The present study was designed to generate data on acute and chronic boron toxicity in support of an update of water quality standards in Illinois, USA. We examined the acute toxicity of boron to eight different freshwater organisms including a fish, an insect, two crustaceans, and four bivalve mollusks. To our knowledge, this is the first study to present data on the toxicity of boron to freshwater mollusks. We also sought to clarify whether hardness or pH affect boron toxicity to aquatic life, and to quantify chronic effect levels in two freshwater species. Sensitivity among the various species ranged widely, with the fathead minnow (Pimephales promelas) being the most sensitive. Neither pH nor hardness had a consistent effect on acute boron toxicity to two crustaceans (Ceriodaphnia dubia and Hyalella azteca), but we observed evidence that chloride reduces boron toxicity to H. azteca. The fathead minnow, while more acutely sensitive than the other species, had a lower acute to chronic ratio than did H. azteca, which had reduced reproduction at 13 mg/L. While we do not know the extent to which the eight tested species represent the range of sensitivities of native but untested species in Illinois, the current water quality standard for Illinois (1 mg/L) is conservative with regard to the native species tested thus far.

  1. Role of endothelin in microvascular dysfunction following percutaneous coronary intervention for non-ST elevation acute coronary syndromes: a single-centre randomised controlled trial

    PubMed Central

    Guddeti, Raviteja R; Prasad, Abhiram; Matsuzawa, Yasushi; Aoki, Tatsuo; Rihal, Charanjit; Holmes, David; Best, Patricia; Lennon, Ryan J; Lerman, Lilach O; Lerman, Amir

    2016-01-01

    Objectives Percutaneous coronary intervention (PCI) for acute coronary syndromes frequently fails to restore myocardial perfusion despite establishing epicardial vessel patency. Endothelin-1 (ET-1) is a potent vasoconstrictor, and its expression is increased in atherosclerosis and after PCI. In this study, we aim to define the role of endothelin in regulating coronary microvascular blood flow and myocardial perfusion following PCI in patients with non-ST elevation acute coronary syndromes (NSTACS), by assessing whether adjunctive therapy with a selective endothelin A (ETA) receptor antagonist acutely improves postprocedural coronary microvascular blood flow. Methods In a randomised, double-blinded, placebo-controlled trial, 23 NSTACS patients were enrolled to receive an intracoronary infusion of placebo (n=11) or BQ-123 (n=12) immediately before PCI. Post-PCI coronary microvascular blood flow and myocardial perfusion were assessed by measuring Doppler-derived average peak velocity (APV), and cardiac biomarker levels were quantified. Results Compared with the placebo group, APV was significantly higher in the drug group immediately after PCI (30 (20, 37) vs 19 (9, 26) cm/s; p=0.03). Hyperaemic APV, measured post-adenosine administration, was higher in the BQ-123 group, but the difference did not achieve statistical significance (56 (48, 72) vs 46 (34, 64) cm/s; p=0.090). Maximum coronary flow reserve postprocedure was not different between the two groups (2.1 (1.6, 2.3) vs 2.5 (1.8, 3.0)). Per cent change in creatine kinase isoenzyme MB from the time of PCI to 8 and 16 hours post-PCI was significantly lower in the drug group compared with the placebo group (−17 (−26, −10) vs 26 (−15, 134); p=0.02 and −17 (−38, 14) vs 107 (2, 446); p=0.007, respectively). Conclusions Endothelin is a mediator of microvascular dysfunction during PCI in NSTACS, and adjunctive selective ETA antagonist may augment myocardial perfusion during PCI. Trial registration number

  2. Executive Dysfunction

    PubMed Central

    Rabinovici, Gil D.; Stephens, Melanie L.; Possin, Katherine L.

    2015-01-01

    Purpose of Review: Executive functions represent a constellation of cognitive abilities that drive goal-oriented behavior and are critical to the ability to adapt to an ever-changing world. This article provides a clinically oriented approach to classifying, localizing, diagnosing, and treating disorders of executive function, which are pervasive in clinical practice. Recent Findings: Executive functions can be split into four distinct components: working memory, inhibition, set shifting, and fluency. These components may be differentially affected in individual patients and act together to guide higher-order cognitive constructs such as planning and organization. Specific bedside and neuropsychological tests can be applied to evaluate components of executive function. While dysexecutive syndromes were first described in patients with frontal lesions, intact executive functioning relies on distributed neural networks that include not only the prefrontal cortex, but also the parietal cortex, basal ganglia, thalamus, and cerebellum. Executive dysfunction arises from injury to any of these regions, their white matter connections, or neurotransmitter systems. Dysexecutive symptoms therefore occur in most neurodegenerative diseases and in many other neurologic, psychiatric, and systemic illnesses. Management approaches are patient specific and should focus on treatment of the underlying cause in parallel with maximizing patient function and safety via occupational therapy and rehabilitation. Summary: Executive dysfunction is extremely common in patients with neurologic disorders. Diagnosis and treatment hinge on familiarity with the clinical components and neuroanatomic correlates of these complex, high-order cognitive processes. PMID:26039846

  3. Pathophysiological regulation of renal SLC22A organic ion transporters in acute kidney injury: pharmacological and toxicological implications.

    PubMed

    Saito, Hideyuki

    2010-01-01

    The kidneys play a primary role in maintaining homeostasis and detoxification of diverse hydrophilic xenobiotics as well as endogenous by-products. Solute carrier (SLC)22A organic ion transporter family members mediate renal excretion of both endogenous and exogenous substances. Thus, the functional and molecular variations of renal SLC22A transporters under acute kidney injury (AKI) have an impact on systemic clearance of their substrate drugs, resulting in altered pharmacokinetics or unexpected adverse events caused by the accumulation of drugs. Recently, there have been significant advances in our understanding of the regulatory mechanisms for transcription, membrane trafficking and/or kidney-specific expression of SLC22A6/OAT1, SLC22A8/OAT3 and SLC22A2/OCT2. Hepatocyte nuclear factor (HNF)-1alpha/beta and HNF-4 appear to play key roles in the transcriptional regulation of OAT1 and OAT3. Furthermore, OAT1 activity/function is modulated via phosphorylation mediated by protein kinase C (PKC) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways. AKI affects renal disposition of organic ions in association with the deteriorated glomerular filtration and tubular transport functions. Thus, dysfunctional regulation of SLC22A transporters during AKI induced by ischemia or toxicants, such as cisplatin, inorganic mercury or uranyl nitrate, cause uremic syndromes or adverse drug reactions. Indoxyl sulfate, a uremic toxin and substrate of OAT1 and OAT3, appears to mediate the progression of AKI evoked by renal ischemia and cisplatin treatment. Precise mechanisms for regulation of the SLC22A transporters in AKI require studies based on the transcription, trafficking, phosphorylation and endogenous factor-dependent modulation. Such analysis will provide a better understanding of the pathophysiological implications of SLC22A transporters.

  4. High CRLF2 expression associates with IKZF1 dysfunction in adult acute lymphoblastic leukemia without CRLF2 rearrangement

    PubMed Central

    Ge, Zheng; Gu, Yan; Zhao, Gang; Li, Jianyong; Chen, Baoan; Han, Qi; Guo, Xing; Liu, Juan; Li, Hui; Yu, Michael D.; Olson, Justin; Steffens, Sadie; Payne, Kimberly J.; Song, Chunhua; Dovat, Sinisa

    2016-01-01

    Overexpression of cytokine receptor-like factor 2 (CRLF2) due to chromosomal rearrangement has been observed in acute lymphoblastic leukemia (ALL) and reported to contribute to oncogenesis and unfavorable outcome in ALL. We studied B-ALL and T-ALL patients without CRLF2 rearrangement and observed that CRLF2 is significantly increased in a subset of these patients. Our study shows that high CRLF2expression correlates with high-risk ALL markers, as well as poor survival. We found that the IKZF1-encoded protein, Ikaros, directly binds to the CRLF2 promoter and regulates CRLF2 expression in leukemia cells. CK2 inhibitor, which can increase Ikaros activity, significantly increases Ikaros binding in ALL cells and suppresses CRLF2 expression in an Ikaros-dependent manner. CRLF2 expression is significantly higher in patients with IKZF1 deletion as compared to patients without IKZF1 deletion. Treatment with CK2 inhibitor also results in an increase in IKZF1 binding to the CRLF2 promoter and suppression of CRLF2 expression in primary ALL cells. We further observed that CK2 inhibitor induces increased H3K9me3 histone modifications in the CRLF2 promoter in ALL cell lines and primary cells. Taken together, our results demonstrate that high expression of CRLF2 correlates with high-risk ALL and short survival in patients without CRLF2 rearrangement. Our results are the first to demonstrate that the IKZF1-encoded Ikaros protein directly suppresses CRLF2 expression through enrichment of H3K9me3 in its promoter region. Our data also suggest that high CRLF2 expression works with the IKZF1 deletion to drive oncogenesis of ALL and has significance in an integrated prognostic model for adult high-risk ALL. PMID:27391346

  5. Dioclea violacea lectin ameliorates oxidative stress and renal dysfunction in an experimental model of acute kidney injury

    PubMed Central

    Freitas, Flavia PS; Porto, Marcella L; Tranhago, Camilla P; Piontkowski, Rogerio; Miguel, Emilio C; Miguel, Thaiz BAR; Martins, Jorge L; Nascimento, Kyria S; Balarini, Camille M; Cavada, Benildo S; Meyrelles, Silvana S; Vasquez, Elisardo C; Gava, Agata L

    2015-01-01

    Acute kidney injury (AKI) is characterized by rapid and potentially reversible decline in renal function; however, the current management for AKI is nonspecific and associated with limited supportive care. Considering the need for more novel therapeutic approaches, we believe that lectins from Dioclea violacea (Dvl), based on their anti-inflammatory properties, could be beneficial for the treatment of AKI induced by renal ischemia/reperfusion (IR). Dvl (1 mg/kg, i.v.) or vehicle (100 µL) was administered to Wistar rats prior to the induction of bilateral renal ischemia (45 min). Following 24 hours of reperfusion, inulin and para-aminohippurate (PAH) clearances were performed to determine glomerular filtration rate (GFR), renal plasma flow (RPF), renal blood flow (RBF) and renal vascular resistance (RVR). Renal inflammation was assessed using myeloperoxidase (MPO) activity. Kidney sections were stained with hematoxylin-eosin to evaluate morphological changes. Intracellular superoxide anions, hydrogen peroxide, peroxynitrite, nitric oxide and apoptosis were analyzed using flow cytometry. IR resulted in diminished GFR, RPF, RBF, and increased RVR; however, these changes were ameliorated in rats receiving Dvl. AKI-induced histomorphological changes, such as tubular dilation, tubular necrosis and proteinaceous casts, were attenuated by Dvl administration. Treatment with Dvl resulted in diminished renal MPO activity, oxidative stress and apoptosis in rats submitted to IR. Our data reveal that Dvl has a protective effect in the kidney, improving renal function after IR injury, probably by reducing neutrophil recruitment and oxidative stress. These results indicate that Dvl can be considered a new therapeutic approach for AKI-induced kidney injury. PMID:26885258

  6. Multi-organ dysfunction in bodybuilding possibly caused by prolonged hypercalcemia due to multi-substance abuse: case report and review of literature.

    PubMed

    Schäfer, C N; Guldager, H; Jørgensen, H L

    2011-01-01

    A 26-year-old male bodybuilder was admitted to the surgical department of a Danish community hospital for hematemesis. During the clinical interview, he revealed that he had recently finished a course of anabolic steroids and erythropoietin. The patient also had a previous history of infections and chronic ulcers due to paraffin-oil injections in both upper arms one year before. Over the course of the next few hours, the patient developed signs of multi-organ dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with temporary anuria, and respiratory insufficiency, and was transferred to the ICU. After manometric monitoring on the patient's upper arms proved difficult, invasive blood pressure monitoring was used and revealed that the patient was in a state of hypertensive crisis. This case of multi-organ dysfunction was possibly caused by multi-substance-induced hypercalcemia.

  7. Orgasmic dysfunction

    MedlinePlus

    Inhibited sexual excitement; Sex - orgasmic dysfunction; Anorgasmia; Sexual dysfunction - orgasmic; Sexual problem - orgasmic ... of knowledge about sexual function Negative feelings about sex (often learned in childhood or teen years) Shyness ...

  8. Whole Adult Organism Transcriptional Profiling of Acute Metal Exposures in Male Zebrafish

    DTIC Science & Technology

    2014-03-10

    adult organism transcriptional profiling of acute metal exposures in male Zebrafish Naissan Hussainzada1, John A Lewis2, Christine E Baer4, Danielle L...fish were pulverized under liquid nitrogen using a SPEX 6750 freezer mill (SPEX Sample Prep, Metuchen, NJ). Total RNA was isolated from the pulverized...advantages and current limitations. Toxicol Pathol 2003, 31(Suppl):62–87. 3. Carvan MJ III, Dalton TP, Stuart GW, Nebert DW: Transgenic zebrafish as

  9. Recombinant human activated protein C attenuates cardiovascular and microcirculatory dysfunction in acute lung injury and septic shock

    PubMed Central

    2010-01-01

    Introduction This prospective, randomized, controlled, experimental animal study looks at the effects of recombinant human activated protein C (rhAPC) on global hemodynamics and microcirculation in ovine acute lung injury (ALI) and septic shock, resulting from smoke inhalation injury. Methods Twenty-one sheep (37 ± 2 kg) were operatively prepared for chronic study and randomly allocated to either the sham, control, or rhAPC group (n = 7 each). The control and rhAPC groups were subjected to insufflation of four sets of 12 breaths of cotton smoke followed by instillation of live Pseudomonas aeruginosa into both lung lobes, according to an established protocol. Healthy sham animals were not subjected to the injury and received only four sets of 12 breaths of room air and instillation of the vehicle (normal saline). rhAPC (24 μg/kg/hour) was intravenously administered from 1 hour post injury until the end of the 24-hour experiment. Regional microvascular blood flow was analyzed using colored microspheres. All sheep were mechanically ventilated with 100% oxygen, and fluid resuscitated with lactated Ringer's solution to maintain hematocrit at baseline levels. Results The rhAPC-associated reduction in heart malondialdehyde (MDA) and heart 3-nitrotyrosine (a reliable indicator of tissue injury) levels occurred parallel to a significant increase in mean arterial pressure and to a significant reduction in heart rate and cardiac output compared with untreated controls that showed a typical hypotensive, hyperdynamic response to the injury (P < 0.05). In addition, rhAPC significantly attenuated the changes in microvascular blood flow to the trachea, kidney, and spleen compared with untreated controls (P < 0.05 each). Blood flow to the ileum and pancreas, however, remained similar between groups. The cerebral blood flow as measured in cerebral cortex, cerebellum, thalamus, pons, and hypothalamus, was significantly increased in untreated controls, due to a loss of cerebral

  10. Acute epidural-like appearance of an encapsulated solid non-organized chronic subdural hematoma.

    PubMed

    Prieto, Ruth; Pascual, José M; Subhi-Issa, Issa; Yus, Miguel

    2010-01-01

    We report the exceptional case of an encapsulated solid non-organized chronic subdural hematoma (SDH) in a 67-year-old woman that was admitted with acute hemiplegia followed by rapid deterioration in consciousness 5 months after a minor head trauma. Computed tomography (CT) showed an extracerebral biconvex shaped hyperdense mass that led to the misdiagnosis of an acute epidural hematoma. Urgent craniotomy revealed an encapsulated mass filled with solid fresh clot in the subdural space. Complete evacuation of this SDH, including both its inner and outer membranes, was achieved, and the patient recovered successfully. Histological analysis confirmed that the content of the hematoma corresponded to a newly formed clot that was enclosed between an inner membrane, composed of two collagen layers, and an outer membrane with a three layered structure. Chronic SDH may seldom present as an encapsulated solid non-organized lesion that consists of a fibrous capsule enclosing a fresh clot and lacking the thick fibrous septations that typically connect the inner and outer membranes of organized chronic SDH. This entity mimics the clinical course and radiological appearance of acute epidural hematomas and should be considered in the differential diagnosis of extracerebral hyperdense biconvex shaped lesions.

  11. Acute Fibrinous and Organizing Pneumonia with Myelodysplastic Syndrome: Corticosteroid Monotherapy Led to Successful Ventilator Weaning

    PubMed Central

    Yamamoto, Mari; Murata, Kengo; Kiriu, Takahiro; Kouzai, Yasuji; Takamori, Mikio

    2016-01-01

    A 62-year-old man with myelodysplastic syndrome (MDS) presented to our hospital with a high fever. Although treatment with broad-spectrum antibiotics was initiated, his respiratory status worsened to the point that he required mechanical ventilation. However, he was successfully treated with a corticosteroid without immunosuppression. Sequential transbronchial lung biopsies revealed abundant fibrin exudate in the alveolar spaces, which was subsequently replaced by fibroblasts, showing that acute fibrinous and organizing pneumonia (AFOP) gradually changes into organizing pneumonia. Our case demonstrated both the efficacy of corticosteroid-monotherapy and the histological course of AFOP. PMID:27803411

  12. Impact of acute kidney injury on distant organ function: recent findings and potential therapeutic targets.

    PubMed

    Doi, Kent; Rabb, Hamid

    2016-03-01

    Acute kidney injury (AKI) is a common complication in critically ill patients and subsequently worsens outcomes. Although many drugs to prevent and treat AKI have shown benefits in preclinical models, no specific agent has been shown to benefit AKI in humans. Moreover, despite remarkable advances in dialysis techniques that enable management of AKI in hemodynamically unstable patients with shock, dialysis-requiring severe AKI is still associated with an unacceptably high mortality rate. Thus, focusing only on kidney damage and loss of renal function has not been sufficient to improve outcomes of patients with AKI. Recent data from basic and clinical research have begun to elucidate complex organ interactions in AKI between kidney and distant organs, including heart, lung, spleen, brain, liver, and gut. This review serves to update the topic of organ cross talk in AKI and focuses on potential therapeutic targets to improve patient outcomes during AKI-associated multiple organ failure.

  13. Overview of Graphical User Interface for ARRBOD (Acute Radiation Risk and BRYNTRN Organ Dose Projection)

    NASA Astrophysics Data System (ADS)

    Kim, Myung-Hee Y.; Hu, Shaowen; Nounu, Hatem; Cucinotta, Francis A.

    Solar particle events (SPEs) pose the risk of acute radiation sickness (ARS) to astronauts be-cause organ doses from large SPEs may reach critical levels during extra vehicular activities (EVAs) or lightly shielded spacecraft. NASA has developed an organ dose projection model of Baryon transport code (BRYNTRN) with an output data processing module of SUMDOSE, and a probabilistic model of acute radiation risk (ARR). BRYNTRN code operation requires extensive input preparation, and the risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. With a graphical user interface (GUI) to handle input and output for BRYNTRN, these response models can be connected easily and correctly to BRYNTRN in a user-friendly way. The GUI for the Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations required for operations of the ARRBOD modules: BRYNTRN, SUMDOSE, and the ARR probabilistic response model. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations direc-torate (MOD), and space biophysics researchers. Assessment of astronauts' organ doses and ARS from the exposure to historically large SPEs is in support of mission design and opera-tion planning to avoid ARS and stay within the current NASA short-term dose limits. The ARRBOD GUI will serve as a proof-of-concept for future integration of other risk projection models for human space applications. We present an overview of the ARRBOD GUI prod-uct, which is a new self-contained product, for the major components of the overall system, subsystem interconnections, and external interfaces.

  14. Overview of Graphical User Interface for ARRBOD (Acute Radiation Risk and BRYNTRN Organ Dose Projection)

    NASA Technical Reports Server (NTRS)

    Kim, Myung-Hee Y.; Hu, Shaowen; Nounu, Hatem N.; Cucinotta, Francis A.

    2010-01-01

    Solar particle events (SPEs) pose the risk of acute radiation sickness (ARS) to astronauts, because organ doses from large SPEs may reach critical levels during extra vehicular activities (EVAs) or lightly shielded spacecraft. NASA has developed an organ dose projection model of Baryon transport code (BRYNTRN) with an output data processing module of SUMDOSE, and a probabilistic model of acute radiation risk (ARR). BRYNTRN code operation requires extensive input preparation, and the risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. With a graphical user interface (GUI) to handle input and output for BRYNTRN, these response models can be connected easily and correctly to BRYNTRN in a user friendly way. The GUI for the Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations required for operations of the ARRBOD modules: BRYNTRN, SUMDOSE, and the ARR probabilistic response model. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. Assessment of astronauts organ doses and ARS from the exposure to historically large SPEs is in support of mission design and operation planning to avoid ARS and stay within the current NASA short-term dose limits. The ARRBOD GUI will serve as a proof-of-concept for future integration of other risk projection models for human space applications. We present an overview of the ARRBOD GUI product, which is a new self-contained product, for the major components of the overall system, subsystem interconnections, and external interfaces.

  15. Acute Radiation Risk and BRYNTRN Organ Dose Projection Graphical User Interface

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.; Hu, Shaowen; Nounu, Hateni N.; Kim, Myung-Hee

    2011-01-01

    The integration of human space applications risk projection models of organ dose and acute radiation risk has been a key problem. NASA has developed an organ dose projection model using the BRYNTRN with SUM DOSE computer codes, and a probabilistic model of Acute Radiation Risk (ARR). The codes BRYNTRN and SUM DOSE are a Baryon transport code and an output data processing code, respectively. The risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. With a graphical user interface (GUI) to handle input and output for BRYNTRN, the response models can be connected easily and correctly to BRYNTRN. A GUI for the ARR and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations, which are required for operations of the ARRBOD modules. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. BRYNTRN code operation requires extensive input preparation. Only a graphical user interface (GUI) can handle input and output for BRYNTRN to the response models easily and correctly. The purpose of the GUI development for ARRBOD is to provide seamless integration of input and output manipulations for the operations of projection modules (BRYNTRN, SLMDOSE, and the ARR probabilistic response model) in assessing the acute risk and the organ doses of significant Solar Particle Events (SPEs). The assessment of astronauts radiation risk from SPE is in support of mission design and operational planning to manage radiation risks in future space missions. The ARRBOD GUI can identify the proper shielding solutions using the gender-specific organ dose assessments in order to avoid ARR symptoms, and to stay within the current NASA short-term dose limits. The quantified evaluation of ARR severities based on any given shielding configuration and a specified EVA or other mission

  16. Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation

    PubMed Central

    2013-01-01

    Introduction Intraspinal grafting of human neural stem cells represents a promising approach to promote recovery of function after spinal trauma. Such a treatment may serve to: I) provide trophic support to improve survival of host neurons; II) improve the structural integrity of the spinal parenchyma by reducing syringomyelia and scarring in trauma-injured regions; and III) provide neuronal populations to potentially form relays with host axons, segmental interneurons, and/or α-motoneurons. Here we characterized the effect of intraspinal grafting of clinical grade human fetal spinal cord-derived neural stem cells (HSSC) on the recovery of neurological function in a rat model of acute lumbar (L3) compression injury. Methods Three-month-old female Sprague–Dawley rats received L3 spinal compression injury. Three days post-injury, animals were randomized and received intraspinal injections of either HSSC, media-only, or no injections. All animals were immunosuppressed with tacrolimus, mycophenolate mofetil, and methylprednisolone acetate from the day of cell grafting and survived for eight weeks. Motor and sensory dysfunction were periodically assessed using open field locomotion scoring, thermal/tactile pain/escape thresholds and myogenic motor evoked potentials. The presence of spasticity was measured by gastrocnemius muscle resistance and electromyography response during computer-controlled ankle rotation. At the end-point, gait (CatWalk), ladder climbing, and single frame analyses were also assessed. Syrinx size, spinal cord dimensions, and extent of scarring were measured by magnetic resonance imaging. Differentiation and integration of grafted cells in the host tissue were validated with immunofluorescence staining using human-specific antibodies. Results Intraspinal grafting of HSSC led to a progressive and significant improvement in lower extremity paw placement, amelioration of spasticity, and normalization in thermal and tactile pain/escape thresholds at

  17. Does Pre-Treatment with High Dose Atorvastatin Prevent Microvascular Dysfunction after Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome?

    PubMed Central

    Lee, Bong-Ki; Nam, Chang-Wook; Doh, Joon-Hyung; Chung, Woo-Young; Cho, Byung-Ryul; Fearon, William F.

    2016-01-01

    Background and Objectives There is controversy surrounding whether or not high dose statin administration before percutaneous coronary intervention (PCI) decreases peri-procedural microvascular injury. We performed a prospective randomized study to investigate the mechanisms and effects of pre-treatment high dose atorvastatin on myocardial damage in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing PCI. Subjects and Methods Seventy seven patients with NSTE-ACS were randomly assigned to either the high dose group (atorvastatin 80 mg loading 12 to 24 h before PCI with a further 40 mg loading 2 h before PCI, n=39) or low dose group (atorvastatin 10 mg administration 12 to 24 h before PCI, n=38). Index of microcirculatory resistance (IMR) was measured after stent implantation. Creatine kinase-myocardial band (CK-MB) and high sensitivity C-reactive protein (CRP) levels were measured before and after PCI. Results The baseline characteristics were not different between the two patient groups. Compared to the low dose group, the high dose group had lower post PCI IMR (14.1±5.0 vs. 19.2±9.3 U, p=0.003). Post PCI CK-MB was also lower in the high dose group (median: 1.40 ng/mL (interquartile range [IQR: 0.75 to 3.45] vs. 4.00 [IQR: 1.70 to 7.37], p=0.002) as was the post-PCI CRP level (0.09 mg/dL [IQR: 0.04 to 0.16] vs. 0.22 [IQR: 0.08 to 0.60], p=0.001). Conclusion Pre-treatment with high dose atorvastatin reduces peri-PCI microvascular dysfunction verified by post-PCI IMR and exerts an immediate anti-inflammatory effect in patients with NSTE-ACS. PMID:27482255

  18. Co-existence of IL7R high and SH2B3 low expression distinguishes a novel high-risk acute lymphoblastic leukemia with Ikaros dysfunction

    PubMed Central

    Ge, Zheng; Gu, Yan; Xiao, Lichan; Han, Qi; Li, Jianyong; Chen, Baoan; Yu, James; Kawasawa, Yuka Imamura; Payne, Kimberly J.; Dovat, Sinisa; Song, Chunhua

    2016-01-01

    Acute lymphoblastic leukemia (ALL) remains the leading cause of cancer-related death in children and young adults. Compared to ALL in children, adult ALL has a much lower cure rate. Therefore, it is important to understand the molecular mechanisms underlying high-risk ALL and to develop therapeutic strategies that specifically target genes or pathways in ALL. Here, we explored the IL7R and SH2B3 expression in adult ALL and found that IL7R is significantly higher and Sh2B3 lower expressed in B-ALL compared to normal bone marrow control, and the IL7RhighSH2B3low is associated with high-risk factors, and with high relapse rate and low disease-free survival rate in the patients. We also found that Ikaros deletion was associated with the IL7RhighSH2B3low expression pattern and Ikaros directly binds the IL7R and SH2B3 promoter, and suppresses IL7R and promotes SH2B3 expression. On the other hand, casein kinase inhibitor, which increases Ikaros function, inhibits IL7R and stimulates SH2B3 expression in an Ikaros dependent manner. Our data indicate that IL7RhighSH2B3low expression distinguishes a novel subset of high-risk B-ALL associated with Ikaros dysfunction, and also suggest the therapeutic potential for treatment that combines casein kinase inhibitor, as an Ikaros activator, with drugs that target the IL7R signaling pathway. PMID:27322554

  19. Utility of Global Longitudinal Strain by Echocardiography to Detect Left Ventricular Dysfunction in Long-Term Adult Survivors of Childhood Lymphoma and Acute Lymphoblastic Leukemia.

    PubMed

    Christiansen, Jon R; Massey, Richard; Dalen, Håvard; Kanellopoulos, Adriani; Hamre, Hanne; Fosså, Sophie D; Ruud, Ellen; Kiserud, Cecilie E; Aakhus, Svend

    2016-08-01

    Measuring left ventricular (LV) global longitudinal strain (GLS) is recommended in screening of long-term cancer survivors for cardiotoxicity. However, there are limited data on GLS in this setting, in particular in survivors with apparently normal LV function without risk factors of impaired GLS. In the present study, we measured GLS in 191 adult survivors of childhood lymphoma or acute lymphoblastic leukemia, with normal LV ejection fraction and fractional shortening (FS) and without known hypertension, diabetes mellitus, myocardial infarction, or stroke. We compared GLS in the survivors with 180 controls. Mean GLS was -19.0 ± 2.2% in the survivor group and -21.4 ± 2.0% in the controls (p <0.001). Impaired GLS, defined as mean - 1.96 SDs in the control group, occurred in 53 of 191 survivors (28%). We included survivors with impaired LV ejection fraction and/or FS or traditional risk factors (n = 231 in all) in multiple regression analyses to explore associations with previous cancer treatment. Survivors treated with mediastinal radiotherapy had an odds ratio of impaired GLS of 5.2 (95% confidence interval 2.2 to 12) compared with other survivors. Survivors treated with cumulative anthracycline doses >300 mg/m(2) had an odds ratio of 4.8 (95% confidence interval 1.7 to 14) of impaired GLS. In conclusion, this study demonstrates a high proportion of LV dysfunction assessed by GLS in apparently healthy adult survivors of childhood cancer. Impaired GLS was associated with previous exposure to mediastinal radiotherapy and high doses of anthracyclines. The prognostic role of measuring GLS in this specific patient population should be examined in prospective studies.

  20. Severe Legionnaires disease complicated by multi-organ dysfunction in a previously healthy patient: a case report

    PubMed Central

    2009-01-01

    A case of a previously healthy lady with community-acquired pneumonia who progressed to severe acute respiratory distress syndrome, acute renal failure, disseminated intravascular coagulation and sepsis is reported. Treatment with antibiotics and various modes of mechanical ventilation in the intensive care unit were successful. A urinary legionella antigen test was positive for Legionella pneumophila. PMID:20062668

  1. Development of Graphical User Interface for ARRBOD (Acute Radiation Risk and BRYNTRN Organ Dose Projection)

    NASA Technical Reports Server (NTRS)

    Kim, Myung-Hee; Hu, Shaowen; Nounu, Hatem N.; Cucinotta, Francis A.

    2010-01-01

    The space radiation environment, particularly solar particle events (SPEs), poses the risk of acute radiation sickness (ARS) to humans; and organ doses from SPE exposure may reach critical levels during extra vehicular activities (EVAs) or within lightly shielded spacecraft. NASA has developed an organ dose projection model using the BRYNTRN with SUMDOSE computer codes, and a probabilistic model of Acute Radiation Risk (ARR). The codes BRYNTRN and SUMDOSE, written in FORTRAN, are a Baryon transport code and an output data processing code, respectively. The ARR code is written in C. The risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. BRYNTRN code operation requires extensive input preparation. With a graphical user interface (GUI) to handle input and output for BRYNTRN, the response models can be connected easily and correctly to BRYNTRN in friendly way. A GUI for the Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations, which are required for operations of the ARRBOD modules: BRYNTRN, SUMDOSE, and the ARR probabilistic response model. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. The ARRBOD GUI will serve as a proof-of-concept example for future integration of other human space applications risk projection models. The current version of the ARRBOD GUI is a new self-contained product and will have follow-on versions, as options are added: 1) human geometries of MAX/FAX in addition to CAM/CAF; 2) shielding distributions for spacecraft, Mars surface and atmosphere; 3) various space environmental and biophysical models; and 4) other response models to be connected to the BRYNTRN. The major components of the overall system, the subsystem interconnections, and external interfaces are described in this

  2. Acute Illness Protocol for Organic Acidemias: Methylmalonic Acidemia and Propionic Acidemia.

    PubMed

    Aldubayan, Saud H; Rodan, Lance H; Berry, Gerard T; Levy, Harvey L

    2017-02-01

    Inborn errors of metabolism (IEM) are genetic disorders that disrupt enzyme activity, cellular transport, or energy production. They are individually rare, but collectively have an incidence of 1:1000. Most patients with IEMs are followed by a physician with expertise in Biochemical Genetics (Metabolism), but may present outside of this setting. Because IEMs can present acutely with life-threatening crises that require specific interventions, it is critical for the emergency medicine physicians, pediatricians, internists, and critical care physicians as well as biochemical geneticists to be familiar with the initial assessment and management of patients with these disorders. Appropriate early care can be lifesaving. This protocol is not designed to replace the expert consultation of a biochemical geneticist but rather to improve early care and increase the level of comfort of the acute care physician with initial management of organic acidemias until specialty consultation is obtained.

  3. Pathophysiology of acute pancreatitis.

    PubMed

    Bhatia, Madhav; Wong, Fei Ling; Cao, Yang; Lau, Hon Yen; Huang, Jiali; Puneet, Padmam; Chevali, Lakshmi

    2005-01-01

    Acute pancreatitis is a common clinical condition. It is a disease of variable severity in which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The exact mechanisms by which diverse etiological factors induce an attack are still unclear. It is generally believed that the earliest events in acute pancreatitis occur within acinar cells. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction. If this inflammatory reaction is marked, it leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. Recent studies have established the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and the resultant MODS. At the same time, recent research has demonstrated the importance of acinar cell death in the form of apoptosis and necrosis as a determinant of pancreatitis severity. In this review, we will discuss about our current understanding of the pathophysiology of acute pancreatitis.

  4. [Intraurethrally applicated alprostadil for the treatment of organic erectile dysfunction in practice: a multicenter clinical monitoring study (noninterventional investigation)].

    PubMed

    Potempal, Axel-Jürg; Potempa, Dirk M; Görlich, Hans Diether; Stolpmann, Rainer M

    2007-01-01

    In a multicenter clinical monitoring study (observation of use investigation according to 67.6 of the German Drug Law), which was conducted between 2003 and 2005 in 105 urological practices in 314 patients with organic erectile dysfunction (ED), efficacy, safety, convenience and acceptance of intraurethral administered alprostadil (CAS 745-65-3; MUSE - Medicated Urethral System for Erection) was studied. 306 patients could statistically be evaluated. The patients were 61.3 +/- 9.2 years old (median+/- SD) (181 patients between 60 and 80 y). The time of ED was from 2 to 120 months with a mean duration of 21.5 +/- 22 months (median+/-SD. Genesis of the ED was in 55 % of the patients a local damage, which followed in 42.8 % a prostate cancer surgery. 46 % of the patients had vascular, 28 % metabolic diseases including diabetes and 11% neural damages. In 51.3% of the patients drugs, which were known to induce ED, were suspected to have caused or partially caused the impairment. The degree of the disturbance was in 93 % of the cases moderate to severe. Alprostadil (MUSE) was applicated three times in doses of 250, 500 or 1000 microg. The dosage of 1000 microg was used for the third application by 65 % of the patients. Very good and good efficacy increased from 45.8% of the patients after the first through 63.7 % after the second to 69.3 % after the third application. In patients after surgery because of prostate cancer very good and good efficacy improved in comparison to the first application about 20% and concerned 53.9 % of the patients after the third application. Sexual intercourse was possible by 67% of the patients after the first, 83 % after the second and 87 % after the third use. Tolerability of alprostadil (MUSE) was very good and good in 90% of the patients. 81.1% intended to continue the treatment. The handling of alprostadil (MUSE) was assessed very good and good by 75%, the acceptance was very good and good in 96% of the patients. In a retrospective

  5. Blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration for patients with multiple organ dysfunction syndrome

    PubMed Central

    Liu, Lu-yi; Zhu, Yong-jian; Li, Xiao-li; Liang, Ya-feng; Liang, Zuo-peng; Xia, Yong-hong

    2012-01-01

    BACKGROUND: Blood hemoperfusion with resin adsorption can clean larger molecules that exceed the molecular weight cutoff of combined continuous veno-venous hemofiltration (CVVH). Hence blood hemoperfusion with resin adsorption combined CVVH (HP+CVVH) has higher ability of mediator clearance, and can improve clinical outcomes in theory. This study aimed to investigate the effect of blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration (HP+CVVH) on plasm cytokines like TNF-α, IL-1β, IL-6, cellular immunity and prognosis in patients with multiple organ dysfunction syndrome (MODS). METHODS: This was a prospective, randomized clinical trial. A total of 30 patients who had been diagnosed with MODS were enrolled in this study. Patients were randomly allocated to routine treatment+HP+CVVH group (treatment group) and routine treatment+only CVVH group (control group). In the treatment group, patients received blood hemoperfusion with resin adsorption for 2 hours, and then received CVVH for 10 hours every day. In the control group, patients received CVVH for 12 hours only every day. The patients in the two groups received blood purification therapy for three days. The plasma of patients in the treatment group was obtained at 0, 2, 12, 24, 26, 36, 48, 50, 60 hours, 5th day, 7th day and 10th day, respectively. The plasma of patients in the control group was obtained at 0, 12, 24, 36, 48, 60 hours, 5th day, 7th day and 10th day, respectively. APACHE II score, T-lymphocytes subpopulations, blood lactate acid concentration, heart rate, breathing rate, and oxygenation index were observed. RESULTS: Plasma cytokines like TNF-α, IL-1β, IL-6 decreased markedly after HP (P<0.01); T-lymphocytes subpopulations CD3+, CD4+, CD8+, CD4+/CD8+ increased after HP+CVVH or only CVVH. The plasma concentrations of TNF-α, IL-1β and IL-6 in the two groups were not markedly different at 12, 36, and 50 hours. But on the 5th day, the plasma concentrations of TNF

  6. Erectile dysfunction.

    PubMed

    Shamloul, Rany; Ghanem, Hussein

    2013-01-12

    Erectile dysfunction is a common clinical entity that affects mainly men older than 40 years. In addition to the classical causes of erectile dysfunction, such as diabetes mellitus and hypertension, several common lifestyle factors, such as obesity, limited or an absence of physical exercise, and lower urinary tract symptoms, have been linked to the development of erectile dysfunction. Substantial steps have been taken in the study of the association between erectile dysfunction and cardiovascular disease. Erectile dysfunction is a strong predictor for coronary artery disease, and cardiovascular assessment of a non-cardiac patient presenting with erectile dysfunction is now recommended. Substantial advances have occurred in the understanding of the pathophysiology of erectile dysfunction that ultimately led to the development of successful oral therapies, namely the phosphodiesterase type 5 inhibitors. However, oral phosphodiesterase type 5 inhibitors have limitations, and present research is thus investigating cutting-edge therapeutic strategies including gene and cell-based technologies with the aim of discovering a cure for erectile dysfunction.

  7. Expression of Organic Anion Transporting Polypeptide 1c1 and Monocarboxylate Transporter 8 in the Rat Placental Barrier and the Compensatory Response to Thyroid Dysfunction

    PubMed Central

    Sun, Yi-na; Liu, Yuan-jun; Zhang, Lu; Ye, Yan; Lin, Lai-xiang; Li, Yong-mei; Yan, Yu-qin; Chen, Zu-pei

    2014-01-01

    Thyroid hormones (THs) must pass from mother to fetus for normal fetal development and require the expression of placental TH transporters. We investigate the compensatory effect of placental organic anion transporting polypeptide 1c1 (Oatp1c1) and monocarboxylate transporter 8 (Mct8) on maternal thyroid dysfunction. We describe the expressions of these two transporters in placental barriers and trophoblastic cell populations in euthyroidism and thyroid dysfunction resulting from differential iodine nutrition at gestation day (GD) 16 and 20, that is, before and after the onset of fetal thyroid function. Immunohistochemistry revealed that in the blood-placenta barrier, these two TH transporters were strongly expressed in the villous interstitial substance and were weakly expressed in trophoblast cells. Levels of Oatp1c1 protein obviously increased in the placental fetal portion during maternal thyroid deficiency at GD16. Under maternal thyroid deficiency after the production of endogenous fetal TH, quantitative PCR analysis revealed down-regulation of Oatp1c1 occurred along with up-regulation of Mct8 in trophoblast cell populations isolated by laser capture microdissection (LCM); this was consistent with the protein levels in the fetal portion of the placenta. In addition, decreased D3 mRNA at GD16 and increased D2 mRNA on two gestational days were observed in trophoblast cells with thyroid dysfunction. However, levels of Oatp1c1 mRNA at GD16 and D3 mRNA at GD20 were too low to be detectable in trophoblast cells. In conclusion, placental Oatp1c1 plays an essential compensatory role when the transplacental passage of maternal THs is insufficient at the stage before the fetal TH production. In addition, the coordinated effects of Oatp1c1, Mct8, D2 and D3 in the placental barrier may regulate both transplacental TH passage and the development of trophoblast cells during thyroid dysfunction throughout the pregnancy. PMID:24763672

  8. Expression of organic anion transporting polypeptide 1c1 and monocarboxylate transporter 8 in the rat placental barrier and the compensatory response to thyroid dysfunction.

    PubMed

    Sun, Yi-na; Liu, Yuan-jun; Zhang, Lu; Ye, Yan; Lin, Lai-xiang; Li, Yong-mei; Yan, Yu-qin; Chen, Zu-pei

    2014-01-01

    Thyroid hormones (THs) must pass from mother to fetus for normal fetal development and require the expression of placental TH transporters. We investigate the compensatory effect of placental organic anion transporting polypeptide 1c1 (Oatp1c1) and monocarboxylate transporter 8 (Mct8) on maternal thyroid dysfunction. We describe the expressions of these two transporters in placental barriers and trophoblastic cell populations in euthyroidism and thyroid dysfunction resulting from differential iodine nutrition at gestation day (GD) 16 and 20, that is, before and after the onset of fetal thyroid function. Immunohistochemistry revealed that in the blood-placenta barrier, these two TH transporters were strongly expressed in the villous interstitial substance and were weakly expressed in trophoblast cells. Levels of Oatp1c1 protein obviously increased in the placental fetal portion during maternal thyroid deficiency at GD16. Under maternal thyroid deficiency after the production of endogenous fetal TH, quantitative PCR analysis revealed down-regulation of Oatp1c1 occurred along with up-regulation of Mct8 in trophoblast cell populations isolated by laser capture microdissection (LCM); this was consistent with the protein levels in the fetal portion of the placenta. In addition, decreased D3 mRNA at GD16 and increased D2 mRNA on two gestational days were observed in trophoblast cells with thyroid dysfunction. However, levels of Oatp1c1 mRNA at GD16 and D3 mRNA at GD20 were too low to be detectable in trophoblast cells. In conclusion, placental Oatp1c1 plays an essential compensatory role when the transplacental passage of maternal THs is insufficient at the stage before the fetal TH production. In addition, the coordinated effects of Oatp1c1, Mct8, D2 and D3 in the placental barrier may regulate both transplacental TH passage and the development of trophoblast cells during thyroid dysfunction throughout the pregnancy.

  9. Ascitic fluid drainage using a peritoneal dialysis catheter to prevent and treat multi-organ dysfunction in veno-occlusive disease in children undergoing hematopoietic stem cell transplantation.

    PubMed

    Parmar, Vijal; Lewis, Malcolm; Shenoy, Mohan; Bonney, Denise; Wynn, Robert

    2017-02-28

    Veno-occlusive disease (VOD), or sinusoidal obstruction syndrome, is a well-recognised, serious complication associated with the chemotherapy conditioning therapy used in hematopoietic stem cell transplantation (HSCT). Fluid management is typically challenging in children with this condition. We describe effective early use of peritoneal dialysis catheters to drain extravascular, intra-abdominal fluid in children with VOD, allowing intravascular fluid administration to preserve renal perfusion and function, preventing multi-organ dysfunction. All but one of the children are long-term survivors, both of their significant VOD and their HSCT. The child that did not survive died from their underlying metabolic illness, not VOD.

  10. Neutrophil Dysfunction in Sepsis

    PubMed Central

    Zhang, Fang; Liu, An-Lei; Gao, Shuang; Ma, Shui; Guo, Shu-Bin

    2016-01-01

    Objective: Sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to infection. In this article, we reviewed the correlation between neutrophil dysfunction and sepsis. Data Sources: Articles published up to May 31, 2016, were selected from the PubMed databases, with the keywords of “neutrophil function”, “neutrophil dysfunction”, and “sepsis”. Study Selection: Articles were obtained and reviewed to analyze the neutrophil function in infection and neutrophil dysfunction in sepsis. Results: We emphasized the diagnosis of sepsis and its limitations. Pathophysiological mechanisms involve a generalized circulatory, immune, coagulopathic, and/or neuroendocrine response to infection. Many studies focused on neutrophil burst or cytokines. Complement activation, impairment of neutrophil migration, and endothelial lesions are involved in this progress. Alterations of cytokines, chemokines, and other mediators contribute to neutrophil dysfunction in sepsis. Conclusions: Sepsis represents a severe derangement of the immune response to infection, resulting in neutrophil dysfunction. Neutrophil dysfunction promotes sepsis and even leads to organ failure. Mechanism studies, clinical practice, and strategies to interrupt dysregulated neutrophil function in sepsis are desperately needed. PMID:27824008

  11. Rapidly Progressive Renal Dysfunction in Two Elderly Patients with Renal Enlargement and Medullary Cystic Kidney Disease-like Acute Tubulointerstitial Injury

    PubMed Central

    Kawamoto, Shinya; Koda, Ryo; Yoshino, Atsunori; Takeda, Tetsuro; Ueda, Yoshihiko

    2016-01-01

    Medullary cystic kidney disease (MCKD) is a hereditary disease associated with bilateral medullary polycysts and interstitial fibrosis. MCKD is typically associated with slowly progressive renal dysfunction. We herein report two rare elderly cases with enlarged kidneys and rapidly progressive renal dysfunction without myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), PR3-ANCA, or anti-glomerular basement membrane (GBM) antibodies. Renal biopsies revealed extensive tubular dilatation and atrophy with interstitial fibrosis consistent with MCKD. Both patients began hemodialysis therapy a few months later. Our cases suggest a MCKD subgroup among elderly patients with an undefined genetic background, rapidly progressive renal dysfunction, and enlarged kidneys. PMID:27746439

  12. A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation

    PubMed Central

    Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A.; Gong, Yongquan; Fischbein, Michael P.; Robbins, Robert C.; Naesens, Maarten

    2013-01-01

    Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design. PMID:24127489

  13. A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation.

    PubMed

    Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A; Gong, Yongquan; Fischbein, Michael P; Robbins, Robert C; Naesens, Maarten; Butte, Atul J; Sarwal, Minnie M

    2013-10-21

    Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design.

  14. Understanding brain dysfunction in sepsis

    PubMed Central

    2013-01-01

    Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood–brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke’s encephalopathy. Modulation of microglial activation, prevention of blood–brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors. PMID:23718252

  15. Erectile Dysfunction

    MedlinePlus

    ... or other heart problems take medications that contain nitrates to help the blood flow better to the ... erectile dysfunction can affect the way that the nitrates work—and cause blood pressure to drop to ...

  16. [Role of heat flow generated by an abdominal cavity in monitoring of acute surgical pathology of abdominal organs].

    PubMed

    Bodiaka, V Iu

    2013-01-01

    Despite of significant development of modern surgery results of treatment of acute diffused peritonitis and acute intestinal obstruction are still unsatisfactory. Successful treatment of these conditions depends considerably on timely and adequate diagnosing as it gives a choice of optimal treatment tactics. Measuring of a human body heat flow in areas of organs affected by pathology in cases of acute diffused peritonitis and acute intestinal obstruction provides a possibility to improve the principles of early differential diagnosing, to form new approaches to treatment tactics and monitoring of general health status of a patient during early postoperative treatment. 47 patient suffering from acute diffused peritonitis and 42 patients suffering from acute intestinal obstruction have been examined; the patients were divided into groups based on abdominal cavity exudates character, intestinal obstruction type and intra-abdominal hypertension grade. Measurement of abdominal cavity heat flow was performed by a contact method with use of thermoelectric medical thermometer. Intra-abdominal hypertension was measured by generally used transvesical method. It has been established that abdominal cavity heat flow correlates with character of abdominal cavity exudates; this is also confirmed by reliable difference between serous peritonitis and fibrinopurulent peritonitis indices. Indices in case of acute intestinal obstruction are lower than ones in case of acute diffused peritonitis as there are no inflammatory changes of peritoneum. Development of intra-abdominal hypertension of grades 3-4 directly influences the heat flow extent; this is explained by accelerated and aggravated pathological changes of inner organs cased by the main disease. Thus, abdominal cavity heat flow fully reflects degree of purulent and inflammatory processes of abdominal cavity organs and can be used for additional diagnosing and clinical course monitoring.

  17. Acute toxicity assessment of Osthol content in bio-pesticides using two aquatic organisms

    PubMed Central

    Yim, Eun-Chae; Kim, Hyeon Joe; Kim, Seong-Jun

    2014-01-01

    Objectives This study focused on the assessment of acute toxicity caused by Osthol, a major component of environment-friendly biological pesticides, by using two aquatic organisms. Methods The assessment of acute toxicity caused by Osthol was conducted in Daphnia magna and by examining the morphological abnormalities in Danio rerio embryos. Results The median effective concentration value of Osthol in D. magna 48 hours after inoculation was 19.3 μM. The median lethal concentration of D. rerio embryo at 96 hours was 30.6 μM. No observed effect concentration and predicted no effect concentration values of Osthol in D. magna and D. rerio were calculated as 5.4 and 0.19 μM, respectively. There was an increase in the morphological abnormalities in D. rerio embryo due to Osthol over time. Coagulation, delayed hatching, yolk sac edema, pericardial edema, and pigmentation were observed in embryos at 24–48 hours. Symptoms of scoliosis and head edema occurred after 72 hours. In addition, bent tails, ocular defects, and symptoms of collapse were observed in fertilized embryo tissue within 96 hours. Ocular defects and pigmentation were the additional symptoms observed in this study. Conclusions Because Osthol showed considerable toxicity levels continuous toxicity evaluation in agro-ecosystems is necessary when bio-pesticides containing Osthol are used. PMID:25518842

  18. Artemia salina as test organism for assessment of acute toxicity of leachate water from landfills.

    PubMed

    Svensson, B M; Mathiasson, L; Mårtensson, L; Bergström, S

    2005-03-01

    Artemia salina has, for the first time, been used as test organism for acute toxicity of leachate water from three landfills (the municipal landfills at Kristianstad, Sweden and Siauliai, Lithuania, and an industrial landfill at Stena fragmenting AB, Halmstad, as well as for leachate from Kristianstad treated in different ways in a pilot plan). Artemia can tolerate the high concentrations of chloride ions found in such waters. Large differences in toxicities were found, the leachate from Siauliai being the most toxic one. To increase the selectivity in the measurements, a fractionation was done by using ion exchange to separate ammonium/ammonia and metal ions from the leachate, and activated carbon adsorbents for organic pollutants. The influence of some metals and phenol compounds on the toxicity was investigated separately. It was found that most of the toxicity emanated from the ammonium/ammonia components in the leachate. However, there was also a significant contribution n from organic pollutants, other than phenol compounds, since separate experiments had in this latter case indicated negligible impact. The concentrations of metals were at a level, shown by separate experiments, where only small contribution to the toxicity could be expected.

  19. Acute fibrinous and organizing pneumonia: A case report and literature review

    PubMed Central

    Xu, Xiao-Yong; Chen, Fei; Chen, Chen; Sun, Hui-Ming; Zhao, Bei-Lei

    2016-01-01

    Acute fibrinous and organizing pneumonia (AFOP) is a rare lung disease with distinct histological characteristics that include the diffuse presence of intra-alveolar fibrin, and the absence of eosinophils and hyaline membrane. In the present study, a case of AFOP that was diagnosed by lung biopsy is described. The patient presented with high fever and a cough with expectoration. Computed tomography of the lung showed the presence of bilateral patchy infiltrates, predominantly in the lower lobes. Histopathological examination of lung biopsy from the lower pulmonary lobe confirmed the pathological diagnosis. The patient showed a poor response to treatment with prednisone. Based on a review of literature pertaining to documented AFOP cases, a summary of the clinical features, radiological characteristics, treatment outcomes and prognoses associated with AFOP are presented. The most common pulmonary symptoms included cough, dyspnea and fever. The primary imaging findings in AFOP were consolidation and ground-glass opacity in the bilateral lung. PMID:28105129

  20. Acute toxicity of a No. 6 fuel oil to marine organisms

    SciTech Connect

    Hollister, T.A.; Ward, G.S.; Parrish, P.R.

    1980-05-01

    The oil tanker Argo Merchant broke up in shoal waters off Nantucket, Massachusetts, in December 1976 and spilled a No. 6 fuel oil containing a No. 2 cutter stock. The US Coast Guard attempted to burn the oil slick at sea, but heavy seas contributed to an unsuccessful operation. Shortly after the spill, acute toxicity tests were performed with five test materials and three saltwater organisms - an alga, a copepod, and a fish. The test materials included a No. 6 fuel oil, a wicking agent, and lighter fluid. The materials were tested singularly and in combination. The three materials were also combined according to instructions from the US Coast Guard, ignited, and the resulting residue tested.

  1. Effects of gabexate mesilate on coagulopathy and organ dysfunction in rats with endotoxemia: a potential use of thrombelastography in endotoxin-induced sepsis.

    PubMed

    Tsai, Hsin-Jung; Ding, Chen; Tsao, Cheng-Ming; Liao, Mei-Hui; Ka, Shuk-Man; Liaw, Wen-Jinn; Wu, Chin-Chen

    2015-03-01

    Sepsis and its associated multiple organ failure are related to high mortality in critical patients. Several studies have reported that gabexate mesilate, a synthetic inhibitor of trypsin-like serine protease, protects tissues/organs against injury in the models of endotoxemia. The aim of this study was to examine whether gabexate mesilate could attenuate coagulopathy and organ dysfunction in lipopolysaccharide (LPS)-induced sepsis model by using thrombelastography (TEG). LPS (7.5  mg/kg/h, intravenouly for 4  h) was administered to male adult Wistar rats. Some of the LPS rats received a continuous infusion of gabexate mesilate (10  mg/kg/h, intravenously for 8.5  h) for 30  min before the LPS administration. Variable parameters of hemodynamics, biochemistry, hemostasis and inflammatory response were measured for 6  h after the LPS infusion. TEG variables (R-time, K-time, α-angle, and maximal amplitude) were also measured. The pretreatment of LPS rats with gabexate mesilate significantly attenuated the lung, liver and kidney dysfunction, consumptive coagulopathy, the increases in serum tumor necrosis factor-α, interleukin-6, plasma thrombin-antithrombin complex and plasminogen activator inhibitor-1, and neutrophils infiltration score in lung, liver and kidney, compared with the LPS alone group. In addition, TEG parameters correlated with tissue and liver injury in the late phase of endotoxemia. In particular, a strong negative correlation between maximal amplitude at 4  h and Ln (lactate dehydrogenase) at 6  h after LPS infusion was noted (r = -0.752, P < 0.001, R = 0.566). These results indicate that beneficial effects of anticoagulants (e.g. gabexate mesilate) in endotoxemia could be monitored by TEG per se.

  2. Endocrine and metabolic dysfunction in yellow perch, Perca flavescens, exposed to organic contaminants and heavy metals in the St. Lawrence River

    SciTech Connect

    Hontela, A.; Duclos, D.; Fortin, R.; Dumont, P.

    1995-04-01

    The endocrine and biochemical responses to the acute stress of capture and handling were investigated in sexually mature and in immature male and female yellow perch, Perca flavescens, from a site contaminated by organic contaminants (PAHs and PCBs) and heavy metals (Hg, Cd, As, and Zn) and from a reference site in the St. Lawrence River. Following a standardized capture and handling stress, fish from the contaminated site did not exhibit the expected physiological stress response observed in fish from the reference site. Blood cortisol and thyroxine levels were lower, and liver glycogen stores were greater in mature males and females, as well as in the immature fish from the contaminated site, compared to the reference site. Fish from the contaminated site also had smaller gonads and lower condition factor. The impaired ability to elevate blood cortisol in response to an acute stress may be used as a biomarker of toxic stress in health assessment of feral fish from polluted environments.

  3. Disease, dysfunction, and synthetic biology.

    PubMed

    Holm, Sune

    2014-08-01

    Theorists analyzing the concept of disease on the basis of the notion of dysfunction consider disease to be dysfunction requiring. More specifically, dysfunction-requiring theories of disease claim that for an individual to be diseased certain biological facts about it must be the case. Disease is not wholly a matter of evaluative attitudes. In this paper, I consider the dysfunction-requiring component of Wakefield's hybrid account of disease in light of the artifactual organisms envisioned by current research in synthetic biology. In particular, I argue that the possibility of artifactual organisms and the case of oncomice and other bred or genetically modified strains of organism constitute a significant objection to Wakefield's etiological account of the dysfunction requirement. I then develop a new alternative understanding of the dysfunction requirement that builds on the organizational theory of function. I conclude that my suggestion is superior to Wakefield's theory because it (a) can accommodate both artifactual and naturally evolved organisms, (b) avoids the possibility of there being a conflict between what an organismic part is supposed to do and the health of the organism, and (c) provides a nonarbitrary and practical way of determining whether dysfunction occurs.

  4. Compensatory and maladaptive responses to cardiac dysfunction.

    PubMed

    Francis, G S; Chu, C

    1994-05-01

    The past few years have witnessed an extraordinary number of important developments in the study of compensatory and maladaptive responses to cardiac dysfunction. It now seems clear that the process whereby the heart remodels in response to left ventricular injury is of paramount importance in the expression of clinical heart failure. There have been parallel attempts by basic scientists and clinical investigators to understand better the fundamental biologic processes that underlie remodeling and to assess numerous new treatments--especially angiotensin-converting enzyme inhibitors. A general consensus seems to be emerging that holds that the response of the heart to acute injury includes a number of highly compensatory and adaptive mechanisms that ultimately become maladaptive and contribute to cardiomegaly and severe congestive heart failure. Such mechanisms undoubtedly include local and systemic release of cytokines, peptides, and neurohormones, and altered loading conditions leading to unusual mechanical forces on cardiac myocytes and other cells of the heart. At the organ level there is hypertrophy, dilatation and growth of the interstitium. Preliminary evidence also suggests there may be some "remodeling" at the cardiac myocyte level. Reduction in peripheral vasodilator reserve is seen in experimental animal models of heart failure. Patients with heart failure also develop an endothelial-dependent form of peripheral vascular dysfunction expressed clinically as an attenuated ability to dilate in response to such stimuli as acetylcholine. The transition point whereby these myocardial and peripheral vascular abnormalities become clearly dysfunctional and contribute toward the full clinical expression of heart failure remains to be further investigated.

  5. Erectile dysfunction.

    PubMed

    Wylie, Kevan

    2008-01-01

    Erectile dysfunction is a common problem affecting sexual function in men. Approximately one in 10 men over the age of 40 is affected by this condition and the incidence is age related. Erectile dysfunction is a sentinel marker for several reversible conditions including peripheral and coronary vascular disease, hypertension and diabetes mellitus. Endothelial dysfunction is a common factor between the disease states. Concurrent conditions such as depression, late-onset hypogonadism, Peyronie's disease and lower urinary tract symptoms may significantly worsen erectile function, other sexual and relationship issues and penis dysmorphophobia. A focused physical examination and baseline laboratory investigations are mandatory. Management consists of initiating modifiable lifestyle changes, psychological and psychosexual/couples interventions and pharmacological and other interventions. In combination and with treatment of concurrent comorbid states, these interventions will often bring about successful resolution of symptoms and avoid the need for surgical interventions.

  6. INTERSPECIES CORRELATION ESTIMATION (ICE) FOR ACUTE TOXICITY TO AQUATIC ORGANISMS AND WILDLIFE. II. USER MANUAL AND SOFTWARE

    EPA Science Inventory

    Asfaw, Amha, Mark R. Ellersieck and Foster L. Mayer. 2003. Interspecies Correlation Estimations (ICE) for Acute Toxicity to Aquatic Organisms and Wildlife. II. User Manual and Software. EPA/600/R-03/106. U.S. Environmental Protection Agency, National Health and Environmental Effe...

  7. PREDICTION OF THE ACUTE TOXICITY OF ORGANIC COMPOUNDS TO THE FATHEAD MINNOW (PIMEPHALES PROMALAS) USING A GROUP CONTRIBUTION METHOD

    EPA Science Inventory

    A group contribution method has been developed to correlate the acute toxicity (96 h LC50) to the fathead minnow (Pimephales promelas) for 379 organic chemicals. Multilinear regression and computational neural networks (CNNs) were used for model building. The multilinear linear m...

  8. Gustatory dysfunction

    PubMed Central

    Maheswaran, T.; Abikshyeet, P.; Sitra, G.; Gokulanathan, S.; Vaithiyanadane, V.; Jeelani, S.

    2014-01-01

    Tastes in humans provide a vital tool for screening soluble chemicals for food evaluation, selection, and avoidance of potentially toxic substances. Taste or gustatory dysfunctions are implicated in loss of appetite, unintended weight loss, malnutrition, and reduced quality of life. Dental practitioners are often the first clinicians to be presented with complaints about taste dysfunction. This brief review provides a summary of the common causes of taste disorders, problems associated with assessing taste function in a clinical setting and management options available to the dental practitioner. PMID:25210380

  9. The Dysfunctions of Bureaucratic Structure.

    ERIC Educational Resources Information Center

    Duttweiler, Patricia Cloud

    1988-01-01

    Numerous dysfunctions result from bureaucratic school organization, including an overemphasis on specialized tasks, routine operating rules, and formal procedures for managing teaching and learning. Such schools are characterized by numerous regulations; formal communications; centralized decision making; and sharp distinctions among…

  10. Acute Toxicity of the Antifouling Compound Butenolide in Non-Target Organisms

    PubMed Central

    Chandramouli, Kondethimmanahalli H.; Xu, Ying; Pan, Ke; Wang, Wen-Xiong; Qian, Pei-Yuan

    2011-01-01

    Butenolide [5-octylfuran-2(5H)-one] is a recently discovered and very promising anti-marine-fouling compound. In this study, the acute toxicity of butenolide was assessed in several non-target organisms, including micro algae, crustaceans, and fish. Results were compared with previously reported results on the effective concentrations used on fouling (target) organisms. According to OECD's guideline, the predicted no effect concentration (PNEC) was 0.168 µg l−1, which was among one of the highest in representative new biocides. Mechanistically, the phenotype of butenolide-treated Danio rerio (zebrafish) embryos was similar to the phenotype of the pro-caspase-3 over-expression mutant with pericardial edema, small eyes, small brains, and increased numbers of apoptotic cells in the bodies of zebrafish embryos. Butenolide also induced apoptosis in HeLa cells, with the activation of c-Jun N-terminal kinases (JNK), Bcl-2 family proteins, and caspases and proteasomes/lysosomes involved in this process. This is the first detailed toxicity and toxicology study on this antifouling compound. PMID:21897857

  11. Acute Toxicity of Endosulfan to the Non-target Organisms Hyalella curvispina and Cnesterodon decemmaculatus.

    PubMed

    Mugni, Hernán; Paracampo, Ariel; Demetrio, Pablo; Scalise, Ana; Solís, Marina; Fanelli, Silvia; Bonetto, Carlos

    2015-09-01

    Pesticide consumption in Argentina has steadily increased over the last two decades, while one of these compounds, namely endosulfan, is commonly found in environmental samples. Also the fish Cnesterodon decemmaculatus and the amphipod Hyalella curvispina are widely distributed in agricultural areas of southern South America. The aim of the present contribution was therefore to determine the acute toxicity of endosulfan to both organisms, and compare it with species sensitivity distributions (SSD) and measured field concentrations. The 48 h-LC50 (with 95 % confidence limits) were 1.8 (1.6-2.1) µg/L for C. decemmaculatus and 16.4 (15.1-17.7) µg/L for H. curvispina. C. decemmaculatus was more sensitive than 74 % of fish based on the SSD. Endosulfan concentrations in stream water reported in the literature were often higher than the C. decemmaculatus LC50. It may hence be concluded that C. decemmaculatus is a suitable sentinel organism for ecotoxicological risk assessment in South America.

  12. Fan1 deficiency results in DNA interstrand cross-link repair defects, enhanced tissue karyomegaly, and organ dysfunction

    PubMed Central

    Thongthip, Supawat; Bellani, Marina; Gregg, Siobhan Q.; Sridhar, Sunandini; Conti, Brooke A.; Chen, Yanglu; Seidman, Michael M.; Smogorzewska, Agata

    2016-01-01

    Deficiency of FANCD2/FANCI-associated nuclease 1 (FAN1) in humans leads to karyomegalic interstitial nephritis (KIN), a rare hereditary kidney disease characterized by chronic renal fibrosis, tubular degeneration, and characteristic polyploid nuclei in multiple tissues. The mechanism of how FAN1 protects cells is largely unknown but is thought to involve FAN1's function in DNA interstrand cross-link (ICL) repair. Here, we describe a Fan1-deficient mouse and show that FAN1 is required for cellular and organismal resistance to ICLs. We show that the ubiquitin-binding zinc finger (UBZ) domain of FAN1, which is needed for interaction with FANCD2, is not required for the initial rapid recruitment of FAN1 to ICLs or for its role in DNA ICL resistance. Epistasis analyses reveal that FAN1 has cross-link repair activities that are independent of the Fanconi anemia proteins and that this activity is redundant with the 5′–3′ exonuclease SNM1A. Karyomegaly becomes prominent in kidneys and livers of Fan1-deficient mice with age, and mice develop liver dysfunction. Treatment of Fan1-deficient mice with ICL-inducing agents results in pronounced thymic and bone marrow hypocellularity and the disappearance of c-kit+ cells. Our results provide insight into the mechanism of FAN1 in ICL repair and demonstrate that the Fan1 mouse model effectively recapitulates the pathological features of human FAN1 deficiency. PMID:26980189

  13. Organ irradiation and combination chemotherapy in treatment of acute lymphocytic leukaemia in children.

    PubMed Central

    Lanzkowsky, P; Shende, A; Aral, I; Saluja, G

    1975-01-01

    Lanzkowsky, P., Shende, A., Aral, I., Saluja, G. (1975). Archives of Disease in Childhood, 50, 685. Organ irradiation and combination chemotherapy in treatment of acute lymphocytic leukaemia in children. A total of 30 consecutive children with acute lymphocytic leukaemia (ALL) were treated from June 1971 until December 1974. Remission was induced with the use of vincristine and prednisone. After induction of remission, cranial irradiation and intrathecal methotrexate were given. Then the liver, spleen, and kidney were irradiated and 6-mercaptopurine, cyclophosphamide, and methotrexate were administered during the maintenance phase. Pulsed doses of vincristine and prednisone were administered at 10- to 12-week intervals. The patients were subdivided into two groups based on their initial white blood cell (WBC) counts: a standard risk group with an initial WBC count of less than 25 000/mm3 (25 X 10(9)/1) and a high risk group with an initial WBC count greater than 25 000/mm3 (25 X 10(9)/1). Of the 30 children entered in this study one standard risk patient died in the induction phase before attaining remission. Analysis of the results is therefore based on the remaining 29 patients, 22 standard risk and 7 high risk patients, who attained complete remission. Survival rates in continuous remission were found to be 43% of the high risk group, 88% for the standard risk group, and 77% for the combined group. Analysis of the data indicates that this therapy is unsatisfactory in high risk ALL. The results to date of this therapy for standard risk are sufficiently encouraging to continue its use in this subgroup of patients. PMID:1059384

  14. Meclofenamate elicits a nephropreventing effect in a rat model of ischemic acute kidney injury by suppressing indoxyl sulfate production and restoring renal organic anion transporters

    PubMed Central

    Saigo, Chika; Nomura, Yui; Yamamoto, Yuko; Sagata, Masataka; Matsunaga, Rika; Jono, Hirofumi; Nishi, Kazuhiko; Saito, Hideyuki

    2014-01-01

    Indoxyl sulfate (IS), a putative low-molecular weight uremic toxin, is excreted in the urine under normal kidney function, but is retained in the circulation and tissues during renal dysfunction in acute kidney injury and chronic kidney disease. IS, which is one of the most potent inducers of oxidative stress in the kidney and cardiovascular system, is enzymatically produced in the liver from indole by cytochrome P450-mediated hydroxylation to indoxyl, followed by sulfotransferase-mediated sulfate conjugation. We used rat liver S9 fraction to identify inhibitors of IS production. After testing several compounds, including phytochemical polyphenols, we identified meclofenamate as a potent inhibitor of IS production with an apparent IC50 value of 1.34 μM. Ischemia/reperfusion (I/R) of rat kidney caused a marked elevation in the serum IS concentration 48 hours after surgery. However, intravenous administration of meclofenamate (10 mg/kg) significantly suppressed this increase in the serum level of IS. Moreover, IS concentrations in both kidney and liver were dramatically elevated by renal I/R treatment, but this increase was blocked by meclofenamate. Serum creatinine and blood urea nitrogen were markedly elevated in rats after renal I/R treatment, but these increases were significantly restored by administration of meclofenamate. Renal expression of both basolateral membrane-localized organic anion transporters rOAT1 and rOAT3 was downregulated by I/R treatment. However, expression of rOAT1 and rOAT3 recovered after administration of meclofenamate, which is associated with the inhibition of I/R-evoked elevation of prostaglandin E2. Our results suggest that meclofenamate inhibits hepatic sulfotransferase-mediated production of IS, thereby suppressing serum and renal accumulation of IS. Meclofenamate also prevents the prostaglandin E2-dependent downregulation of rOAT1 and rOAT3 expression. In conclusion, meclofenamate was found to elicit a nephropreventive effect in

  15. Erectile dysfunction

    PubMed Central

    2011-01-01

    Introduction Erectile dysfunction may affect 30% to 50% of men aged 40 to 70 years, with age, smoking, and obesity being the main risk factors, although 20% of cases have psychological causes. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of phosphodiesterase inhibitors in men with erectile dysfunction of any cause? What are the effects of phosphodiesterase inhibitors on erectile dysfunction in men with diabetes, with cardiovascular disease, with spinal cord injury, and with prostate cancer or undergoing prostatectomy? What are the effects of drug treatments other than phosphodiesterase inhibitors in men with erectile dysfunction of any cause? What are the effects of devices, psychological/behavioural treatments, and alternative treatments in men with erectile dysfunction of any cause? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 81 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: alprostadil (intracavernosal, intraurethral, topical), cognitive behavioural therapy, ginseng, papaverine, papaverine plus phentolamine (bimix), papaverine plus phentolamine plus alprostadil (trimix), penile prostheses, phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil), psychosexual counselling, vacuum devices, and yohimbine. PMID:21711956

  16. Transplantation of Endothelial Cells to Mitigate Acute and Chronic Radiation Injury to Vital Organs.

    PubMed

    Rafii, Shahin; Ginsberg, Michael; Scandura, Joseph; Butler, Jason M; Ding, Bi-Sen

    2016-08-01

    Current therapeutic approaches for treatment of exposure to radiation involve the use of antioxidants, chelating agents, recombinant growth factors and transplantation of stem cells (e.g., hematopoietic stem cell transplantation). However, exposure to high-dose radiation is associated with severe damage to the vasculature of vital organs, often leading to impaired healing, tissue necrosis, thrombosis and defective regeneration caused by aberrant fibrosis. It is very unlikely that infusion of protective chemicals will reverse severe damage to the vascular endothelial cells (ECs). The role of irradiated vasculature in mediating acute and chronic radiation syndromes has not been fully appreciated or well studied. New approaches are necessary to replace and reconstitute ECs in organs that are irreversibly damaged by radiation. We have set forth the novel concept that ECs provide paracrine signals, also known as angiocrine signals, which not only promote healing of irradiated tissue but also direct organ regeneration without provoking fibrosis. We have developed innovative technologies that enable manufacturing and banking of human GMP-grade ECs. These ECs can be transplanted intravenously to home to and engraft to injured tissues where they augment organ repair, while preventing maladaptive fibrosis. In the past, therapeutic transplantation of ECs was not possible due to a shortage of availability of suitable donor cell sources and preclinical models, a lack of understanding of the immune privilege of ECs, and inadequate methodologies for expansion and banking of engraftable ECs. Recent advances made by our group as well as other laboratories have breached the most significant of these obstacles with the development of technologies to manufacture clinical-scale quantities of GMP-grade and human ECs in culture, including genetically diverse reprogrammed human amniotic cells into vascular ECs (rAC-VECs) or human pluripotent stem cells into vascular ECs (iVECs). This

  17. Transplantation of Endothelial Cells to Mitigate Acute and Chronic Radiation Injury to Vital Organs

    PubMed Central

    Rafii, Shahin; Ginsberg, Michael; Scandura, Joseph; Butler, Jason M.; Ding, Bi-Sen

    2016-01-01

    Current therapeutic approaches for treatment of exposure to radiation involve the use of antioxidants, chelating agents, recombinant growth factors and transplantation of stem cells (e.g., hematopoietic stem cell transplantation). However, exposure to high-dose radiation is associated with severe damage to the vasculature of vital organs, often leading to impaired healing, tissue necrosis, thrombosis and defective regeneration caused by aberrant fibrosis. It is very unlikely that infusion of protective chemicals will reverse severe damage to the vascular endothelial cells (ECs). The role of irradiated vasculature in mediating acute and chronic radiation syndromes has not been fully appreciated or well studied. New approaches are necessary to replace and reconstitute ECs in organs that are irreversibly damaged by radiation. We have set forth the novel concept that ECs provide paracrine signals, also known as angiocrine signals, which not only promote healing of irradiated tissue but also direct organ regeneration without provoking fibrosis. We have developed innovative technologies that enable manufacturing and banking of human GMP-grade ECs. These ECs can be transplanted intravenously to home to and engraft to injured tissues where they augment organ repair, while preventing maladaptive fibrosis. In the past, therapeutic transplantation of ECs was not possible due to a shortage of availability of suitable donor cell sources and preclinical models, a lack of understanding of the immune privilege of ECs, and inadequate methodologies for expansion and banking of engraftable ECs. Recent advances made by our group as well as other laboratories have breached the most significant of these obstacles with the development of technologies to manufacture clinical-scale quantities of GMP-grade and human ECs in culture, including genetically diverse reprogrammed human amniotic cells into vascular ECs (rAC-VECs) or human pluripotent stem cells into vascular ECs (iVECs). This

  18. Acute impact of erythromycin and tetracycline on the kinetics of nitrification and organic carbon removal in mixed microbial culture.

    PubMed

    Katipoglu-Yazan, Tugce; Pala-Ozkok, Ilke; Ubay-Cokgor, Emine; Orhon, Derin

    2013-09-01

    The study evaluated acute impact of erythromycin and tetracycline on nitrification and organic carbon removal kinetics in mixed microbial culture. Acclimated biomass was obtained from a fill and draw reactor fed with peptone mixture selected as synthetic substrate and operated at a sludge age of 10 days. Acute inhibition was tested in batch reactors involving a control unit started solely with substrate and the others with additional doses of each antibiotic. Modeling indicated that both steps of nitrification were totally blocked by erythromycin. Tetracycline inhibited and retarded nitrification kinetics at 50 mg/L and stopped nitrite oxidation at 200 mg/L, leading to nitrite accumulation. Both antibiotics also affected organic carbon removal by inducing partial inactivation of the heterotrophic community in the culture, increased substrate storage and accelerated endogenous respiration, with a relatively slight impact on heterotrophic growth. Major inhibitory effect was on process stoichiometry, leading to partial utilization of organic substrate.

  19. Kölliker's Organ and the Development of Spontaneous Activity in the Auditory System: Implications for Hearing Dysfunction

    PubMed Central

    Dayaratne, M. W. Nishani; Vlajkovic, Srdjan M.; Lipski, Janusz; Thorne, Peter R.

    2014-01-01

    Prior to the “onset of hearing,” developing cochlear inner hair cells (IHCs) and primary auditory neurons undergo experience-independent activity, which is thought to be important in retaining and refining neural connections in the absence of sound. One of the major hypotheses regarding the origin of such activity involves a group of columnar epithelial supporting cells forming Kölliker's organ, which is only present during this critical period of auditory development. There is strong evidence for a purinergic signalling mechanism underlying such activity. ATP released through connexin hemichannels may activate P2 purinergic receptors in both Kölliker's organ and the adjacent IHCs, leading to generation of electrical activity throughout the auditory system. However, recent work has suggested an alternative origin, by demonstrating the ability of IHCs to generate this spontaneous activity without activation by ATP. Regardless, developmental abnormalities of Kölliker's organ may lead to congenital hearing loss, considering that mutations in ion channels (hemichannels, gap junctions, and calcium channels) involved in Kölliker's organ activity share strong links with such types of deafness. PMID:25210710

  20. Attenuation of endotoxin-induced multiple organ dysfunction by 1-amino-2-hydroxy-guanidine, a potent inhibitor of inducible nitric oxide synthase.

    PubMed Central

    Ruetten, H.; Southan, G. J.; Abate, A.; Thiemermann, C.

    1996-01-01

    1. We have investigated the effects of (i) several guanidines on the activity of the inducible isoform of nitric oxide (NO) synthase (iNOS) in murine cultured macrophages and rat aortic vascular smooth muscle cells (RASM); and (ii) 1-amino-2-hydroxy-guanidine, the most potent inhibitor of iNOS activity discovered, on haemodynamics, multiple organ (liver, renal, and pancreas) dysfunction and iNOS activity in rats with endotoxic shock. 2. The synthesized guanidine analogues caused concentration-dependent inhibitions of the increase in nitrite formation caused by lipopolysaccaride (LPS, 1 microgram ml-1) in J774.2 macrophages and RASM cells with the following rank order of potency: 1-amino-2-hydroxy-guanidine > 1-amino-2-methyl-guanidine > 1-amino-1-methyl-guanidine > 1-amino-1,2-dimethyl-guanidine. Interestingly, 1-amino-2-hydroxy-guanidine (IC50: J774.2, 68 microM; RASM, 114 microM) was more potent in inhibiting nitrite formation caused by LPS than NG-methyl-L-arginine, but less potent than aminoethyl-isothiourea. 3. In the anaesthetized rat, LPS caused a fall in mean arterial blood pressure (MAP) from 115 +/- 4 mmHg (time 0) to 98 +/- 5 mmHg at 2 h (P < 0.05, n = 10) and 69 +/- 5 mmHg at 6 h (P < 0.05, n = 10). The pressor effect of noradrenaline (NA, 1 mg kg-1, i.v.) was also significantly reduced at 1 to 6 h after LPS (vascular hyporeactivity). Treatment of LPS-rats with 1-amino-2-hydroxy-guanidine (10 mg kg-1, i.v. plus 10 mg kg-1 h-1 starting at 2 h after LPS) prevented the delayed hypotension and vascular hyporeactivity seen in LPS-rats. However, 1-amino-2-hydroxy-guanidine had no effect on either MAP or the pressor effect elicited by NA in rats infused with saline rather than LPS. 4. Endotoxaemia for 6 h caused a significant rise in the serum levels of aspartate or alanine aminotransferase (i.e. GOT or GPT) and bilirubin, and hence, liver dysfunction. Treatment of LPS-rats with 1-amino-2-hydroxy-guanidine significantly attenuated the liver dysfunction caused

  1. [Investigation of the effects of cytoflavin on symptoms of depression and autonomic dysfunction in patients with organic depressive disorder].

    PubMed

    Gudkova, A N; Osinovskaia, N A; Polunina, A G; Gekht, A B

    2013-01-01

    The present observational study addressed effects of cytoflavin as an adjunctive nootropic therapy in patients with organic depressive disorder (F06.36). 54 female and 46 male in-patients were included into the study. All patients received standard antidepressant therapy (controls) and 48 patients additionally received 2 pills of cytoflavin twice per day. Age, gender distribution, education and severity of depression were equal in cytoflavin and control groups. The follow-up assessment at discharge showed a significantly more pronounced decline in the severity of depression symptoms in patients receiving cytoflavin in comparison with the controls. Importantly, the effect of cytoflavin on the depression symptoms was prominent only in females. Moreover, women receiving cytoflavin demonstrated the more pronounced normalization of autonomic regulation in comparison with control women. The present results allow to recommend cytoflavin in dose 4 pills daily as an adjunctive therapy in female patients with organic depressive disorder.

  2. Effects of subfornical organ lesions on acutely induced thirst and salt appetite

    NASA Technical Reports Server (NTRS)

    Thunhorst, R. L.; Beltz, T. G.; Johnson, A. K.

    1999-01-01

    We examined the role of the subfornical organ (SFO) in stimulating thirst and salt appetite using two procedures that initiate water and sodium ingestion within 1-2 h of extracellular fluid depletion. The first procedure used injections of a diuretic (furosemide, 10 mg/kg sc) and a vasodilator (minoxidil, 1-3 mg/kg ia) to produce hypotension concurrently with hypovolemia. The resulting water and sodium intakes were inhibited by intravenous administration of ANG II receptor antagonist (sarthran, 8 micrograms . kg(-1). min(-1)) or angiotensin-converting enzyme inhibitor (captopril, 2.5 mg/h). The second procedure used injections of furosemide (10 mg/kg sc) and a low dose of captopril (5 mg/kg sc) to initiate water and sodium ingestion upon formation of ANG II in the brain. Electrolytic lesions of the SFO greatly reduced the water intakes, and nearly abolished the sodium intakes, produced by these relatively acute treatments. These results contrast with earlier findings showing little effect of SFO lesions on sodium ingestion after longer-term extracellular fluid depletion.

  3. Whole adult organism transcriptional profiling of acute metal exposures in male Zebrafish

    PubMed Central

    2014-01-01

    Background A convergence of technological breakthroughs in the past decade has facilitated the development of rapid screening tools for biomarkers of toxicant exposure and effect. Platforms using the whole adult organism to evaluate the genome-wide response to toxicants are especially attractive. Recent work demonstrates the feasibility of this approach in vertebrates using the experimentally robust zebrafish model. In the present study, we evaluated gene expression changes in whole adult male zebrafish following an acute 24 hr high dose exposure to three metals with known human health risks. Male adult zebrafish were exposed to nickel chloride, cobalt chloride or sodium dichromate concentrations corresponding to their respective 96 hr LC20, LC40 and LC60. Histopathology was performed on a subset of metal-exposed zebrafish to phenotypically anchor transcriptional changes associated with each metal. Results Comparative analysis identified subsets of differentially expressed transcripts both overlapping and unique to each metal. Application of gene ontology (GO) and transcription factor (TF) enrichment algorithms revealed a number of key biological processes perturbed by metal poisonings and the master transcriptional regulators mediating gene expression changes. Metal poisoning differentially activated biological processes associated with ribosome biogenesis, proteosomal degradation, and p53 signaling cascades, while repressing oxygen-generating pathways associated with amino acid and lipid metabolism. Despite appreciable effects on gene regulation, nickel poisoning did not induce any morphological alterations in male zebrafish organs and tissues. Histopathological effects of cobalt remained confined to the olfactory system, while chromium targeted the gills, pharynx, and intestinal mucosa. A number of enriched transcription factors mediated the observed gene response to metal poisoning, including known targets such as p53, HIF1α, and the myc oncogene, and novel

  4. [A case of rupture of the left ventricle free wall with papillary muscle dysfunction following acute myocardial infarction, operated on successfully].

    PubMed

    de Lima, R; Perdigão, C; Neves, L; Cravino, J; Dantas, M; Bordalo, A; Pais, F; Diogo, A N; Ferreira, R; Ribeiro, C

    1990-09-01

    The authors present a case of left ventricular free wall rupture post acute myocardial infarction, associated with mitral papillary posterior muscle necrosis, operated by infartectomy and mitral valvular protesis replacement. They refer the various complications occurred during the hospital staying, and discuss its medical and surgical approach. The patient was discharged alive and six months after the infarction keeps a moderate activity.

  5. [Multiple organ failure complicating a severe acute necrotising pancreatitis secondary of a severe hypertriglyceridemia: a case report].

    PubMed

    Degardin, J; Pons, B; Ardisson, F; Gallego, J-P; Thiery, G

    2013-09-01

    We report the case of a 42-year-old man admitted for a multi-organ failure with a coma, a hemodynamic instability, a respiratory distress syndrome, an acute renal failure and a thrombocytopenia. The blood samples highlighted a milky serum and allowed to diagnose an acute pancreatitis associated with a major dyslipidemia: hypertriglyceridemia 11,800 mg/dL and hypercholesterolemia 1195 mg/dL. The CT-scans do not reveal any cerebral abnormalities but highlighted pancreatic lesions without biliary obstruction. A multi-organ failure complicating a severe acute pancreatitis secondary of a major hypertriglyceridemia was mentioned. Despite the absence of clear guidelines, a session of plasma exchange was started in emergency. Symptomatic treatment with protective ventilation, vasopressors, continuous heparin and insulin was continued. The clinical and biological course was good in parallel of the normalization of lipid abnormalities. The patient was discharged at day 17 with a lipid-lowering therapy. We discuss the various treatments available for the management of acute pancreatitis complicating a severe hypertriglyceridemia and their actual relevance in the absence of clear recommendations.

  6. Etoricoxib-induced life-threatening hyperkalemia and acute kidney dysfunction against the background of telmisartan and a low sodium diet

    PubMed Central

    Dash, Suresh Chandra

    2010-01-01

    Drug-induced hyperkalemia is not uncommon and may be life-threatening when presenting acutely in the emergency department. We present a case of severe hyperkalemia precipitated acutely by etoricoxib in a patient who was on telmisartan and a low sodium (potassium chloride-rich) diet. A 75-year-old male with a past medical history of well-controlled diabetes and hypertension was prescribed etoricoxib (90 mg daily) for 3 days for musculoskeletal backache. He had been taking his routine medications including telmisartan and a potassium-rich salt substitute for many years, without any recent change in dosage or quantity. There was evidence of microalbuminurea; however, the renal functions and electrolytes prior to starting etoricoxib were normal. He presented to the emergency department with signs and symptoms of life-threatening hyperkalemia (serum potassium 7.7 mEq/dl), accelerated hypertension, congestive heart failure, pulmonary edema and acute renal failure. Acute medical management and withholding all drugs that could cause hyperkalemia improved his serum potassium levels over 24 h and renal parameters within 5 days. All the other drugs except etoricoxib were restarted under observation over 8 weeks with no recurrence of the acute episode. Non-steroidal analgesics and other COX-2 inhibitors (rofecoxib and celecoxib) have been known to precipitate renal failure and hyperkalemia specially in patients at risk for the same; although not unexpected, this may be the first reported case of life-threatening hyperkalemia precipitated by etoricoxib in a previously stable patient having increased risk of renal failure and hyperkalemia. PMID:21373319

  7. [Principles of intensive care in severe acute pancreatitis in 2008].

    PubMed

    Darvas, Katalin; Futó, Judit; Okrös, Ilona; Gondos, Tibor; Csomós, Akos; Kupcsulik, Péter

    2008-11-23

    Acute pancreatitis is a dynamic, often progressive disease; 14-20% require intensive care in its severe form due to multiorgan dysfunction and/or failure. This review was created using systematic literature review of articles published on this subject in the last 5 years. The outcome of severe acute pancreatitis is determined by the inflammatory response and multiorgan dysfunction - the prognostic scores (Acute Physiology and Chronic Health Evaluation, Glasgow Prognostic Index, Sepsis-related Organ Failure Assessment, Multi Organ Dysfunction Syndrome Scale, Ranson Scale) can be used to determine outcome. Clinical signs (age, coexisting diseases, confusion, obesity) and biochemistry values (serum amylase, lipase, C-reactive protein, procalcitonin, creatinine, urea, calcium) have important prognostic roles as well. Early organ failure increases the risk of late abdominal complications and mortality. Intensive care can provide appropriate multi-function patient monitoring which helps in early recognition of complications and appropriate target-controlled treatment. Treatment of severe acute pancreatitis aims at reducing systemic inflammatory response and multiorgan dysfunction and, on the other side, at increasing the anti-inflammatory response. Oral starvation for 24-48 hours is effective in reducing the exocrine activity of the pancreas; the efficacy of protease inhibitors is questionable. Early intravascular volume resuscitation and stable haemodynamics improve microcirculation. Early oxygen therapy and mechanical ventilation provide adequate oxygenation. Electrolyte and acid-base control can be as important as tight glucose control. Adequate pain relief can be achieved by thoracic epidural catheterization. Early enteral nutrition with immunonutrition should be used. There is evidence that affecting the coagulation cascade by activated protein C can play a role in reducing the inflammatory response. The complex therapy of acute pancreatitis includes appropriate

  8. Association of dioxin and other persistent organic pollutants (POPs) with diabetes: epidemiological evidence and new mechanisms of beta cell dysfunction.

    PubMed

    De Tata, Vincenzo

    2014-05-05

    The worldwide explosion of the rates of diabetes and other metabolic diseases in the last few decades cannot be fully explained only by changes in the prevalence of classical lifestyle-related risk factors, such as physical inactivity and poor diet. For this reason, it has been recently proposed that other "nontraditional" risk factors could contribute to the diabetes epidemics. In particular, an increasing number of reports indicate that chronic exposure to and accumulation of a low concentration of environmental pollutants (especially the so-called persistent organic pollutants (POPs)) within the body might be associated with diabetogenesis. In this review, the epidemiological evidence suggesting a relationship between dioxin and other POPs exposure and diabetes incidence will be summarized, and some recent developments on the possible underlying mechanisms, with particular reference to dioxin, will be presented and discussed.

  9. Association of Dioxin and Other Persistent Organic Pollutants (POPs) with Diabetes: Epidemiological Evidence and New Mechanisms of Beta Cell Dysfunction

    PubMed Central

    De Tata, Vincenzo

    2014-01-01

    The worldwide explosion of the rates of diabetes and other metabolic diseases in the last few decades cannot be fully explained only by changes in the prevalence of classical lifestyle-related risk factors, such as physical inactivity and poor diet. For this reason, it has been recently proposed that other “nontraditional” risk factors could contribute to the diabetes epidemics. In particular, an increasing number of reports indicate that chronic exposure to and accumulation of a low concentration of environmental pollutants (especially the so-called persistent organic pollutants (POPs)) within the body might be associated with diabetogenesis. In this review, the epidemiological evidence suggesting a relationship between dioxin and other POPs exposure and diabetes incidence will be summarized, and some recent developments on the possible underlying mechanisms, with particular reference to dioxin, will be presented and discussed. PMID:24802877

  10. Association of low non-invasive near-infrared spectroscopic measurements during initial trauma resuscitation with future development of multiple organ dysfunction

    PubMed Central

    Nicks, Bret A.; Campos, Kevin M.; Bozeman, William P.

    2015-01-01

    BACKGROUND: Near-infrared spectroscopy (NIRS) non-invasively monitors muscle tissue oxygen saturation (StO2). It may provide a continuous noninvasive measurement to identify occult hypoperfusion, guide resuscitation, and predict the development of multiple organ dysfunction (MOD) after severe trauma. We evaluated the correlation between initial StO2 and the development of MOD in multi-trauma patients. METHODS: Patients presenting to our urban, academic, Level I Trauma Center/Emergency Department and meeting standardized trauma-team activation criteria were enrolled in this prospective trial. NIRS monitoring was initiated immediately on arrival with collection of StO2 at the thenar eminence and continued up to 24 hours for those admitted to the Trauma Intensive Care Unit (TICU). Standardized resuscitation laboratory measures and clinical evaluation tools were collected. The primary outcome was the association between initial StO2 and the development of MOD within the first 24 hours based on a MOD score of 6 or greater. Descriptive statistical analyses were performed; numeric means, multivariate regression and rank sum comparisons were utilized. Clinicians were blinded from the StO2 values. RESULTS: Over a 14 month period, 78 patients were enrolled. Mean age was 40.9 years (SD 18.2), 84.4% were male, 76.9% had a blunt trauma mechanism and mean injury severity score (ISS) was 18.5 (SD 12.9). Of the 78 patients, 26 (33.3%) developed MOD within the first 24 hours. The MOD patients had mean initial StO2 values of 53.3 (SD 10.3), significantly lower than those of non-MOD patients 61.1 (SD 10.0); P=0.002. The mean ISS among MOD patients was 29.9 (SD 11.5), significantly higher than that of non-MODS patients, 12.1 (SD 9.1) (P<0.0001). The mean shock index (SI) among MOD patients was 0.92 (SD 0.28), also significantly higher than that of non-MODS patients, 0.73 (SD 0.19) (P=0.0007). Lactate values were not significantly different between groups. CONCLUSION: Non

  11. Primary Graft Dysfunction after Lung Transplantation

    PubMed Central

    Altun, Gülbin Töre; Arslantaş, Mustafa Kemal; Cinel, İsmail

    2015-01-01

    Primary graft dysfunction (PGD) is a severe form of acute lung injury that is a major cause of early morbidity and mortality encountered after lung transplantation. PGD is diagnosed by pulmonary oedema with diffuse alveolar damage that manifests clinically as progressive hypoxemia with radiographic pulmonary infiltrates. Inflammatory and immunological response caused by ischaemia and reperfusion is important with regard to pathophysiology. PGD affects short- and long-term outcomes, the donor organ is the leading factor affecting these adverse ramifications. To minimize the risk of PGD, reduction of lung ischaemia time, reperfusion optimisation, prostaglandin level regulation, haemodynamic control, hormone replacement therapy, ventilator management are carried out; for research regarding donor lung preparation strategies, certain procedures are recommended. In this review, recent updates in epidemiology, pathophysiology, molecular and genetic biomarkers and technical developments affecting PGD are described. PMID:27366539

  12. Erectile dysfunction.

    PubMed

    McMahon, C G

    2014-01-01

    In the past 30 years, advances in basic science have been instrumental in the evolution of the male sexual health treatment paradigm from a psychosexual model to a new model, which includes oral and intracavernosal injection pharmacotherapy, vacuum constriction devices and penile prostheses for the treatment of erectile dysfunction. This progress has coincided with an increased understanding of the nature of male sexual health problems, and epidemiological data that confirm that these problems are widely prevalent and the source of considerable morbidity, both for individuals and within relationships.

  13. The acute toxicity of thallium to freshwater organisms: Implications for risk assessment.

    PubMed

    Tatsi, Kristi; Turner, Andrew; Handy, Richard D; Shaw, Benjamin J

    2015-12-01

    The acute toxicity of Tl(I) to the microalga, Pseudokirchneriella subcapitata, the planktonic crustaceans, Daphnia magna and Daphnia pulex, and early-life stage of the zebrafish, Danio rerio, has been studied according to OECD protocols. Toxicological end-point concentrations for the microalga ranged from 17 μg l(-1) for a 72 h EyC25 (yield inhibition) to 80 μg l(-1) for a 72 h ErC50 (growth inhibition). Daphnia were less sensitive to Tl, with 48 h EC50s of about 1000 μg l(-1) and 1200 μg l(-1) for D. magna and D. pulex, respectively; however, end-point concentrations were reduced considerably (to about 510 μg l(-1) and 730 μg l(-1), respectively) when experiments were repeated in dechlorinated Plymouth tap water (rather than OECD medium). The 96 h LC50 for D. rerio was 870 μg l(-1) but a variety of sub-lethal effects, including enlargement of yolk sac and reduction in heart beat rate, were observed when larvae were exposed to lower concentrations. Based on these results, a predicted no effect concentration (PNEC) for Tl in freshwaters of 0.087 μg l(-1) is proposed. The PNEC is an order of magnitude lower than the only (Canadian) water quality guideline for Tl that appears to exist, and is lower than Tl concentrations reported in freshwaters impacted by historical or contemporary metal mining. Our results are also consistent with previous studies that employ different organisms and end-points in that Tl toxicity is dependent on the concentration of K+, the biogeochemical analogue of Tl+. Accordingly, regulation of Tl in the freshwater environment should factor in the relative abundance of K.

  14. Atypical Structural Connectome Organization and Cognitive Impairment in Young Survivors of Acute Lymphoblastic Leukemia.

    PubMed

    Kesler, Shelli R; Gugel, Meike; Huston-Warren, Emily; Watson, Christa

    2016-05-01

    Survivors of pediatric acute lymphoblastic leukemia (ALL) are at increased risk for cognitive impairments that disrupt everyday functioning and decrease quality of life. The specific biological mechanisms underlying cognitive impairment following ALL remain largely unclear, but previous studies consistently demonstrate significant white matter pathology. We aimed to extend this literature by examining the organization of the white matter connectome in young patients with a history of ALL treated with chemotherapy only. We applied graph theoretical analysis to diffusion tensor imaging obtained from 31 survivors of ALL age 5-19 years and 39 matched healthy controls. Results indicated significantly lower small-worldness (p = 0.007) and network clustering coefficient (p = 0.019), as well as greater cognitive impairment (p = 0.027) in the ALL group. Regional analysis indicated that clustered connectivity in parietal, frontal, hippocampal, amygdalar, thalamic, and occipital regions was altered in the ALL group. Random forest analysis revealed a model of connectome and demographic variables that could automatically classify survivors of ALL as having cognitive impairment or not (accuracy = 0.89, p < 0.0001). These findings provide further evidence of brain injury in young survivors of ALL, even those without a history of central nervous system (CNS) disease or cranial radiation. Efficiency of local information processing, reorganization of hub connectivity, and cognitive reserve may contribute to cognitive outcome in these children. Certain connectome properties showed U-shaped relationships with cognitive impairment suggesting an optimal range of regional connectivity.

  15. Dysfunction of Organic Anion Transporting Polypeptide 1a1 Alters Intestinal Bacteria and Bile Acid Metabolism in Mice

    PubMed Central

    Zhang, Youcai; Limaye, Pallavi B.; Lehman-McKeeman, Lois D.; Klaassen, Curtis D.

    2012-01-01

    Organic anion transporting polypeptide 1a1 (Oatp1a1) is predominantly expressed in liver and is able to transport bile acids (BAs) in vitro. Male Oatp1a1-null mice have increased concentrations of taurodeoxycholic acid (TDCA), a secondary BA generated by intestinal bacteria, in both serum and livers. Therefore, in the present study, BA concentrations and intestinal bacteria in wild-type (WT) and Oatp1a1-null mice were quantified to investigate whether the increase of secondary BAs in Oatp1a1-null mice is due to alterations in intestinal bacteria. The data demonstrate that Oatp1a1-null mice : (1) have similar bile flow and BA concentrations in bile as WT mice; (2) have a markedly different BA composition in the intestinal contents, with a decrease in conjugated BAs and an increase in unconjugated BAs; (3) have BAs in the feces that are more deconjugated, desulfated, 7-dehydroxylated, 3-epimerized, and oxidized, but less 7-epimerized; (4) have 10-fold more bacteria in the small intestine, and 2-fold more bacteria in the large intestine which is majorly due to a 200% increase in Bacteroides and a 30% reduction in Firmicutes; and (5) have a different urinary excretion of bacteria-related metabolites than WT mice. In conclusion, the present study for the first time established that lack of a liver transporter (Oatp1a1) markedly alters the intestinal environment in mice, namely the bacteria composition. PMID:22496825

  16. Lipopolysaccharide-Induced Neutrophil Dysfunction Following Transjugular Intrahepatic Portosystemic Stent Shunt (TIPSS) Insertion is Associated with Organ Failure and Mortality

    PubMed Central

    Macnaughtan, Jane; Mookerjee, Rajeshwar P.; Jalan, Rajiv

    2017-01-01

    Systemic lipopolysaccharide (LPS) is implicated in increasing mortality in patients with alcoholic hepatitis but the underlying mechanisms are not well characterised. The objective of this study was to characterise neutrophil function, LPS and cytokine concentrations within the splanchnic circulation of alcoholic cirrhotic patients undergoing TIPSS insertion for variceal haemorrhage and correlate this with outcome. 26 patients with alcoholic cirrhosis and variceal haemorrhage were studied prior to and 1-hour after TIPSS insertion. Neutrophil function, LPS and cytokine concentrations were determined in arterial, hepatic venous (HV) and portal venous blood (PV). Significantly higher LPS concentrations and neutrophil reactive oxidant species (ROS) production were observed in PV vs HV blood. Cross-incubation of HV plasma with PV neutrophils resulted in reduced ROS production. Insertion of TIPSS was associated with a significant increase in arterial LPS concentrations and deterioration in neutrophil phagocytosis. Number of organ failures and arterial IL-6 concentrations at presentation were associated with increased mortality. The portal circulation has a distinct immunological milieu characterised by a pathological neutrophil phenotype and an anti-inflammatory cytokine profile associated with heightened LPS levels. TIPSS insertion renders this neutrophil functional defect systemic, associated with an increase in arterial LPS and a susceptibility to sepsis. PMID:28051160

  17. Aerobic exercise acutely prevents the endothelial dysfunction induced by mental stress among subjects with metabolic syndrome: the role of shear rate.

    PubMed

    Sales, Allan R K; Fernandes, Igor A; Rocha, Natália G; Costa, Lucas S; Rocha, Helena N M; Mattos, João D M; Vianna, Lauro C; Silva, Bruno M; Nóbrega, Antonio C L

    2014-04-01

    Mental stress induces transient endothelial dysfunction, which is an important finding for subjects at cardiometabolic risk. Thus, we tested whether aerobic exercise prevents this dysfunction among subjects with metabolic syndrome (MetS) and whether an increase in shear rate during exercise plays a role in this phenomenon. Subjects with MetS participated in two protocols. In protocol 1 (n = 16), endothelial function was assessed using brachial artery flow-mediated dilation (FMD). Subjects then underwent a mental stress test followed by either 40 min of leg cycling or rest across two randomized sessions. FMD was assessed again at 30 and 60 min after exercise or rest, with a second mental stress test in between. Mental stress reduced FMD at 30 and 60 min after the rest session (baseline: 7.7 ± 0.4%, 30 min: 5.4 ± 0.5%, and 60 min: 3.9 ± 0.5%, P < 0.05 vs. baseline), whereas exercise prevented this reduction (baseline: 7.5 ± 0.4%, 30 min: 7.2 ± 0.7%, and 60 min: 8.7 ± 0.8%, P > 0.05 vs. baseline). Protocol 2 (n = 5) was similar to protocol 1 except that the first period of mental stress was followed by either exercise in which the brachial artery shear rate was attenuated via forearm cuff inflation or exercise without a cuff. Noncuffed exercise prevented the reduction in FMD (baseline: 7.5 ± 0.7%, 30 min: 7.0 ± 0.7%, and 60 min: 8.7 ± 0.8%, P > 0.05 vs. baseline), whereas cuffed exercise failed to prevent this reduction (baseline: 7.5 ± 0.6%, 30 min: 5.4 ± 0.8%, and 60 min: 4.1 ± 0.9%, P < 0.05 vs. baseline). In conclusion, exercise prevented mental stress-induced endothelial dysfunction among subjects with MetS, and an increase in shear rate during exercise mediated this effect.

  18. Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems

    PubMed Central

    Dainiak, Nicholas; Gent, Robert Nicolas; Carr, Zhanat; Schneider, Rita; Bader, Judith; Buglova, Elena; Chao, Nelson; Coleman, C. Norman; Ganser, Arnold; Gorin, Claude; Hauer-Jensen, Martin; Huff, L. Andrew; Lillis-Hearne, Patricia; Maekawa, Kazuhiko; Nemhauser, Jeffrey; Powles, Ray; Schünemann, Holger; Shapiro, Alla; Stenke, Leif; Valverde, Nelson; Weinstock, David; White, Douglas; Albanese, Joseph; Meineke, Viktor

    2013-01-01

    Objectives The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature. Methods English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made. Results No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/ orshock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak

  19. Acute toxicity to freshwater organisms of antiparasitic drugs for veterinary use.

    PubMed

    Yoshimura, Haruo; Endoh, Yuuko S

    2005-02-01

    The acute toxicity of five antiparasitic drugs used in the veterinary field-amprolium hydrochloride (APH), bithionol (BT), levamisole hydrochloride (LVH), pyrimethamine (PYM) and trichlorfon (TRC)-to the aquatic organisms Oryzias latipes, Daphnia magna, and Brachionus calyciflorus was examined. The toxicity test with O. latipes was conducted in accordance with the OECD Guidelines for the Testing of Chemicals (1993) to determine the 24-, 48-, 72-, and 96-h LC(50) values. In addition, 24- and 48-h EC(50) values for D. magna and a 24-h EC(50) for B. calyciflorus were determined with the DAPHTOXKIT F(trade mark) magna (Creasel, Belgium) and the ROTOXKIT F(trade mark) (Creasel, Belgium), respectively. High-performance liquid chromatographic analysis revealed that APH, LVH, and PYM were stable in water, but BT was unstable, decreasing by 84% on average at 24 h. TRC rapidly decomposed, with only 0.7% of the initial concentration remaining after 96 h, forming dichlorvos. The toxicity of TRC to O. latipes was determined in two ways: exposure to the same medicated water for 96 h (static test) and exposure to medicated water replaced every 24 h (semistatic test). AMP, LVM, and PYM were tested in the static condition, and BT was tested in the semistatic condition. BT was most toxic to O. latipes, with a 96-h LC(50) of 0.24 mg L(-1), followed by PYM, with a 96-h LC(50) of 5.6 mg L(-1). The 24-, 48-, 72-, and 96-h LC(50) values of TRC in the static test were 92.0, 45.2, 29.5, and 17.6 mg L(-1), respectively, which tended to be lower than those in the semistatic test, especially late in the observation period. D. magna was the most susceptible to TRC, with a 48-h EC(50) as low as 0.00026 mg L(-1). The 48-h EC(50) values of BT, PYM, and LVH for D. magna were 0.3, 5.2, and 64.0 mg L(-1), respectively. B. calyciflorus was the most susceptible to BT, with an EC(50) of 0.063 mg L(-1), followed by PYM, with an EC(50) of 15.0 mg L(-1). Among the test compounds, APH was the least toxic

  20. Cerium Oxide Nanoparticles in Lung Acutely Induce Oxidative Stress, Inflammation, and DNA Damage in Various Organs of Mice

    PubMed Central

    Yuvaraju, Priya; Beegam, Sumaya; Fahim, Mohamed A.; Ali, Badreldin H.

    2017-01-01

    CeO2 nanoparticles (CeO2 NPs) which are used as a diesel fuel additive are emitted in the particulate phase in the exhaust, posing a health concern. However, limited information exists regarding the in vivo acute toxicity of CeO2 NPs on multiple organs. Presently, we investigated the acute (24 h) effects of intratracheally instilled CeO2 NPs in mice (0.5 mg/kg) on oxidative stress, inflammation, and DNA damage in major organs including lung, heart, liver, kidneys, spleen, and brain. Lipid peroxidation measured by malondialdehyde production was increased in the lungs only, and reactive oxygen species were increased in the lung, heart, kidney, and brain. Superoxide dismutase activity was decreased in the lung, liver, and kidney, whereas glutathione increased in lung but it decreased in the kidney. Total nitric oxide was increased in the lung and spleen but it decreased in the heart. Tumour necrosis factor-α increased in all organs studied. Interleukin- (IL-) 6 increased in the lung, heart, liver, kidney, and spleen. IL-1β augmented in the lung, heart, kidney, and spleen. Moreover, CeO2 NPs induced DNA damage, assessed by COMET assay, in all organs studied. Collectively, these findings indicate that pulmonary exposure to CeO2 NPs causes oxidative stress, inflammation, and DNA damage in multiple organs. PMID:28392888

  1. Interventional effects of da-cheng-qi decoction on enteric nerve system in a rat model of multiple organ dysfunction syndrome.

    PubMed

    Xie, Ming-Zheng; Luo, Peng; Ma, Bin; Li, Lu; Wang, De-Hua; Qi, Qing-Hui

    2015-01-01

    In this study, we investigate the morphologic changes of enteric nerve system (ENS) and the expression of neurotransmitters, acetylcholine (ACh), substance P (SP), vasoactive intestinal peptide (VIP) and nitric oxide synthase (NOS), in small bowel of rats undergoing multiple organ dysfunction syndrome (MODS). Undergoing MODS, fluorescence integral optical density (IOD) value of enteric nerve fibers were significantly decreased (P<0.05), and the network structure of ENS was destroyed. The expression of ACh, SP, VIP and NOS was inhibited, IOD value of the four neurotransmitters was significantly decreased (P<0.05). After intervention of DCQD, the fluorescence IOD value of enteric nerves were significantly increased (P<0.05), and the network structure of ENS was repaired. The expression of ACh, SP, VIP and NOS was recovered, fluorescence IOD value of the four neurotransmitters was significantly increased (P<0.05). In conclusion, the gastrointestinal motility disorders undergoing MODS may be closely related to the morphology destroy of ENS and down regulation of neurotransmitters (ACh, SP, VIP and NOS) expression. DCQD could promote gastrointestinal motility through protecting the morphology of ENS and up regulation of neurotransmitters (ACh, SP, VIP and NOS) expression.

  2. Determinants of oxygen and carbon dioxide transfer during extracorporeal membrane oxygenation in an experimental model of multiple organ dysfunction syndrome.

    PubMed

    Park, Marcelo; Costa, Eduardo Leite Vieira; Maciel, Alexandre Toledo; Silva, Débora Prudêncio E; Friedrich, Natalia; Barbosa, Edzangela Vasconcelos Santos; Hirota, Adriana Sayuri; Schettino, Guilherme; Azevedo, Luciano Cesar Pontes

    2013-01-01

    Extracorporeal membrane oxygenation (ECMO) has gained renewed interest in the treatment of respiratory failure since the advent of the modern polymethylpentene membranes. Limited information exists, however, on the performance of these membranes in terms of gas transfers during multiple organ failure (MOF). We investigated determinants of oxygen and carbon dioxide transfer as well as biochemical alterations after the circulation of blood through the circuit in a pig model under ECMO support before and after induction of MOF. A predefined sequence of blood and sweep flows was tested before and after the induction of MOF with fecal peritonitis and saline lavage lung injury. In the multivariate analysis, oxygen transfer had a positive association with blood flow (slope = 66, P<0.001) and a negative association with pre-membrane PaCO(2) (slope = -0.96, P = 0.001) and SatO(2) (slope = -1.7, P<0.001). Carbon dioxide transfer had a positive association with blood flow (slope = 17, P<0.001), gas flow (slope = 33, P<0.001), pre-membrane PaCO(2) (slope = 1.2, P<0.001) and a negative association with the hemoglobin (slope = -3.478, P = 0.042). We found an increase in pH in the baseline from 7.50[7.46,7.54] to 7.60[7.55,7.65] (P<0.001), and during the MOF from 7.19[6.92,7.32] to 7.41[7.13,7.5] (P<0.001). Likewise, the PCO(2) fell in the baseline from 35 [32,39] to 25 [22,27] mmHg (P<0.001), and during the MOF from 59 [47,91] to 34 [28,45] mmHg (P<0.001). In conclusion, both oxygen and carbon dioxide transfers were significantly determined by blood flow. Oxygen transfer was modulated by the pre-membrane SatO(2) and CO(2), while carbon dioxide transfer was affected by the gas flow, pre-membrane CO(2) and hemoglobin.

  3. High-Grade Acute Organ Toxicity as a Positive Prognostic Factor in Primary Radiochemotherapy for Anal Carcinoma

    SciTech Connect

    Wolff, Hendrik Andreas; Raus, Ismene; Jung, Klaus; Schueler, Phillip; Herrmann, Markus Karl; Hennies, Steffen; Vorwerk, Hilke; Hille, Andrea; Hess, Clemens Friedrich; Christiansen, Hans

    2011-04-01

    Purpose: To test for a possible correlation between high-grade acute organ toxicity during primary radiochemotherapy and treatment outcome for patients with anal carcinoma. Methods and Materials: From 1991 to 2009, 72 patients with anal carcinoma were treated at our department (10 patients had stage I, 28 patients had stage II, 11 patients had stage IIIA, and 13 patients had stage IIIB cancer [Union Internationale Contre le Cancer criteria]). All patients received normofractionated (1.8 Gy/day, five times/week) whole-pelvis irradiation including iliac and inguinal lymph nodes with a cumulative dose of 50.4 Gy. Concomitant chemotherapy regimen consisted of two cycles of 5-fluorouracil (1,000 mg/m{sup 2}total body surface area (TBSA)/day as continuous intravenous infusion on days 1-4 and 29-32) and mitomycin C (10 mg/m{sup 2}/TBSA, intravenously on days 1 and 29). Toxicity during treatment was monitored weekly, and any incidence of Common Toxicity Criteria (CTC) grade of {>=}3 for skin reaction, cystitis, proctitis, or enteritis was assessed as high-grade acute organ toxicity for later analysis. Results: We found significant correlation between high-grade acute organ toxicity and overall survival, locoregional control, and stoma-free survival, which was independent in multivariate analysis from other possible prognostic factors: patients with a CTC acute organ toxicity grade of {>=}3 had a 5-year overall survival rate of 97% compared to 30% in patients without (p < 0.01, multivariate analysis; 97% vs. 48%, p = 0.03 for locoregional control, and 95% vs. 59%, p = 0.05 for stoma-free survival). Conclusions: Our data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, since high-grade acute organ toxicity during radiochemotherapy showed itself to be an independent prognostic marker in our patient population. This hypothesis should be further analyzed by using biomolecular and clinical levels in future clinical trials.

  4. Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs.

    PubMed

    Fish, Brian L; Gao, Feng; Narayanan, Jayashree; Bergom, Carmen; Jacobs, Elizabeth R; Cohen, Eric P; Moulder, John E; Orschell, Christie M; Medhora, Meetha

    2016-11-01

    The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ~24 mg m d started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg d from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated.

  5. Parasympathetic stimulation via the vagus nerve prevents systemic organ dysfunction by abrogating gut injury and lymph toxicity in trauma and hemorrhagic shock.

    PubMed

    Levy, Gal; Fishman, Jordan E; Xu, Dazhong; Chandler, Benjamin T J; Feketova, Eleonora; Dong, Wei; Qin, Yong; Alli, Vamsi; Ulloa, Luis; Deitch, Edwin A

    2013-01-01

    We tested if vagus nerve stimulation (VNS) would prevent gut injury, mesenteric lymph toxicity, and systemic multiple organ dysfunction syndrome following trauma-hemorrhagic shock (T/HS). Four groups of experiments were performed. The first tested whether VNS (5 V for 10 min) would protect against T/HS-induced increases in gut and lung permeability as well as neutrophil priming. In the second experiment, mesenteric lymph was collected from rats subjected to T/HS or trauma-sham shock with or without VNS and then injected into naive mice to assess its biologic activity. Lung permeability, neutrophil priming, and red blood cell deformability were measured. Next, the role of the spleen in VNS-mediated protection was tested by measuring gut and lung injury in splenectomized rats subjected to sham or actual VNS. Lastly, the ability of nicotine to replicate the gut-protective effect of VNS was tested. Vagus nerve stimulation protected against T/HS-induced gut injury, lung injury, and neutrophil priming (P < 0.05). Not only did VNS limit organ injury after T/HS, but in contrast to the mesenteric lymph collected from the sham-VNS T/HS rats, the mesenteric lymph from the VNS T/HS rats did not cause lung injury, neutrophil priming, or loss of red blood cell deformability (P < 0.05) when injected into naive mice. Removal of the spleen did not prevent the protective effects of VNS on gut or lung injury after T/HS. Similar to VNS, the administration of nicotine also protected the gut from injury after T/HS. Vagus nerve stimulation prevents T/HS-induced gut injury, lung injury, neutrophil priming, and the production of biologically active mesenteric lymph. This protective effect of VNS was not dependent on the spleen but appeared to involve a cholinergic nicotinic receptor, because its beneficial effects could be replicated with nicotine.

  6. Hyperferritinemia in the critically ill child with secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction syndrome/macrophage activation syndrome: what is the treatment?

    PubMed Central

    2012-01-01

    Introduction Hyperferritinemia is associated with increased mortality in pediatric sepsis, multiple organ dysfunction syndrome (MODS), and critical illness. The International Histiocyte Society has recommended that children with hyperferritinemia and secondary hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) should be treated with the same immunosuppressant/cytotoxic therapies used to treat primary HLH. We hypothesized that patients with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS can be successfully treated with a less immunosuppressant approach than is recommended for primary HLH. Methods We conducted a multi-center cohort study of children in Turkish Pediatric Intensive Care units with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS treated with less immunosuppression (plasma exchange and intravenous immunoglobulin or methyl prednisolone) or with the primary HLH protocol (plasma exchange and dexamethasone or cyclosporine A and/or etoposide). The primary outcome assessed was hospital survival. Results Twenty-three children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS were enrolled (median ferritin = 6341 μg/dL, median number of organ failures = 5). Univariate and multivariate analyses demonstrated that use of plasma exchange and methyl prednisolone or intravenous immunoglobulin (n = 17, survival 100%) was associated with improved survival compared to plasma exchange and dexamethasone and/or cyclosporine and/or etoposide (n = 6, survival 50%) (P = 0.002). Conclusions Children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS can be successfully treated with plasma exchange, intravenous immunoglobulin, and methylprednisone. Randomized trials are required to evaluate if the HLH-94 protocol is helpful or harmful compared to this less immune suppressive and cytotoxic approach in this specific population. PMID:22715953

  7. Pathophysiology of pulmonary complications of acute pancreatitis

    PubMed Central

    Browne, George W; Pitchumoni, CS

    2006-01-01

    Acute pancreatitis in its severe form is complicated by multiple organ system dysfunction, most importantly by pulmonary complications which include hypoxia, acute respiratory distress syndrome, atelectasis, and pleural effusion. The pathogenesis of some of the above complications is attributed to the production of noxious cytokines. Clinically significant is the early onset of pleural effusion, which heralds a poor outcome of acute pancreatitis. The role of circulating trypsin, phospholipase A2, platelet activating factor, release of free fatty acids, chemoattractants such as tumor necrsosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, IL-8, fMet-leu-phe (a bacterial wall product), nitric oxide, substance P, and macrophage inhibitor factor is currently studied. The hope is that future management of acute pancreatitis with a better understanding of the pathogenesis of lung injury will be directed against the production of noxious cytokines. PMID:17131469

  8. Changes in numbers of leukocytes in immune organs of juvenile coho salmon after acute stress or cortisol treatment

    USGS Publications Warehouse

    Maule, Alec G.; Schreck, Carl B.

    1990-01-01

    We examined the effects of acute stress and cortisol treatment on the number of leukocytes (normalized for fish body weight) in the blood, thymus, spleen, and anterior kidney of juvenile coho salmon Oncorhynchus kisutch. In acutely stressed or cortisol-fed fish, the numbers of leukocytes increased significantly in the thymus and anterior kidney, and decreased significantly in blood and spleen within 1 d after treatment. Numbers of cells in the anterior kidney, blood, and spleen returned to control levels by 3 d after treatment, but cell numbers in the thymus remained significantly greater than control values until 3–7 d after acute stress. Although dietary cortisol resulted in increased plasma cortisol titers and caused the same changes in leukocyte distribution as those caused by acute stress, the magnitude or duration of elevated cortisol levels and leukocyte numbers were not correlated. These results suggest that, although increased plasma cortisol titers induced by stress may be involved in the change in number of cells in various immune organs, factors other than cortisol are involved as well.

  9. Gonadal dysfunction in systemic diseases.

    PubMed

    Karagiannis, Asterios; Harsoulis, Faidon

    2005-04-01

    Gonadal function is significantly affected in many acute and chronic systemic diseases. As the function of the testes and the ovaries is determined by the integrity of the hypothalamic-pituitary-gonadal axis, it is obvious that a systemic disease may affect one or more levels of the axis in such a manner that the gonadal dysfunction may have various clinical and laboratory manifestations. In this brief review, the most common disturbances seen in the main systemic diseases will be discussed.

  10. Clinical Safety and Efficacy of Nilotinib or Dasatinib in Patients with Newly Diagnosed Chronic-Phase Chronic Myelogenous Leukemia and Pre-existing Liver and/or Renal Dysfunction

    PubMed Central

    Sasaki, Koji; Lahoti, Amit; Jabbour, Elias; Jain, Preetesh; Pierce, Sherry; Borthakur, Gautam; Daver, Naval; Kadia, Tapan; Pemmaraju, Naveen; Ferrajoli, Alessandra; O’Brien, Susan; Kantarjian, Hagop; Cortes, Jorge

    2016-01-01

    Summary BACKGROUND The safety and efficacy of frontline nilotinib and dasatinib in newly diagnosed chronic-phase chronic myelogenous leukemia (CML-CP) patients with pre-existing liver and/or renal dysfunction are unknown. PATIENTS and METHODS We analyzed adverse event rates, response rates, and survival rates of 215 CML-CP patients with or without renal and/or liver dysfunction who were treated with front-line nilotinib (108 patients) or dasatinib (107 patients). RESULTS Overall median follow-up was 49 months. At baseline, 6 (6%) dasatinib-treated patients had mild renal dysfunction and 13 (12%) had mild liver dysfunction. Eight (7%) nilotinib-treated patients had mild renal dysfunction, 1 (1%) had moderate renal dysfunction, and 9 (8%) mild liver dysfunction. There were no significant differences in the rates of complete cytogenetic response, major molecular response, or MR4.5 between organ function cohorts. Dasatinib- or nilotinib- treated patients with baseline renal dysfunction had a higher incidence of transient reversible acute kidney injury (p=0.011; p<0.001), and nilotinib-treated patients with renal dysfunction had a higher incidence of bleeding (p<0.001). CONCLUSION CML-CP patients with mild to moderate renal or liver dysfunction can be safely treated with frontline dasatinib or nilotinib and can achieve response rates similar to those of CML-CP patients with normal organ function. PMID:26796981

  11. Outcome in noncritically ill patients with acute kidney injury requiring dialysis: Effects of differing medical staffs and organizations.

    PubMed

    Fagugli, Riccardo Maria; Patera, Francesco; Battistoni, Sara; Tripepi, Giovanni

    2016-07-01

    Acute kidney injury requiring dialysis (AKI-D) treatment has significantly increased in incidence over the years, with more than 400 new cases per million population/y, 2/3 of which concern noncritically ill patients. In these patients, there are little data on mortality or on information of care organization and its impact on outcome. Specialty training and integrated teams, as well as a high volume of activity, seem to be linked to better hospital outcome. The study investigates mortality of patients admitted to and in-care of nephrology (NEPHROpts), a closed-staff organization, and to other medical wards (MEDpts), representing a model of open-staff organization.This is a single center, case-control cohort study derived from a prospective epidemiology investigation on patients with AKI-D admitted to or in-care of the Hospital of Perugia during the period 2007 to 2014. Noncritically ill AKI-D patients were analyzed: inclusion and exclusion criteria were defined to avoid possible bias on the cause of hospital admittance and comorbidities, and a propensity score (PS) matching was performed.Six hundred fifty-four noncritically ill patients were observed and 296 fulfilled inclusion/exclusion criteria. PS matching resulted in 2 groups: 100 NEPHROpts and 100 MEDpts. Characteristics, comorbidities, acute kidney injury causes, risk-injury-failure acute kidney injury criteria, and simplified acute physiology score (SAPS 2) were similar. Mortality was 36%, and a difference was reported between NEPHROpts and MEDpts (20% vs 52%, χ = 23.2, P < 0.001). Patients who died differed in age, serum creatinine, blood urea nitrogen/s.Creatinine ratio, dialysis urea reduction rate (URR), SAPS 2 and Charlson score; they presented a higher rate of heart disease, and a larger proportion required noradrenaline/dopamine for shock. After correction for mortality risk factors, multivariate Cox analysis revealed that site of treatment (medical vs nephrology wards) represents an

  12. Effect of lycopene against cisplatin-induced acute renal injury in rats: organic anion and cation transporters evaluation.

    PubMed

    Erman, Fazilet; Tuzcu, Mehmet; Orhan, Cemal; Sahin, Nurhan; Sahin, Kazim

    2014-04-01

    In the present study, we investigated the effects of lycopene on the expression of organic anion transporters (OATs), organic cation transporters (OCTs), and multidrug resistance-associated proteins (MRPs) of cisplatin-induced nephrotoxicity in rats. Twenty-eight 8-week-old Wistar rats were divided into four groups: control, lycopene-treated (6 mg/kg BW by oral gavage), cisplatin-treated (7 mg/kg BW, IP), and lycopene in combination with cisplatin-treated groups. In the presence of cisplatin, serum urea nitrogen (urea-N) (48.5 vs. 124.3 mg/dl) and creatinine (0.29 vs. 1.37 mg/dl) levels and the kidney efflux transporters MRP2 and MRP4 levels were significantly increased, whereas OAT1, OAT3, OCT1, and OCT2 levels in kidney were decreased in the treated rats compared with normal control rats. However, administration of lycopene in combination with cisplatin resulted in a reduction in the serum urea-N (124.3 vs. 62.4) and creatinine (1.37 vs. 0.40) levels and the kidney efflux transporters MRP2 and MRP4 proteins in the kidneys. Administration of lycopene to acute renal injury-induced rats largely upregulated the organic anion transporters (OAT1 and 3) and organic cation transporters (OCT1 and 2) to decrease the side effects of cisplatin. The present study suggests that lycopene synergizes with its nephroprotective effect against cisplatin-induced acute kidney injury in rats.

  13. [Postoperative pain management. Aims and organization of a strategy for postoperative acute pain therapy].

    PubMed

    Nolli, M; Nicosia, F

    2000-09-01

    The Health Services, not only the Italian one, is under pressure because of request for improving treatment quality and the financial need for reorganization and cost-saving. It's required a rationalization of intervention, together with a careful choice of the best and cheapest techniques and the demonstration of their efficacy. The anaesthesia service activity, in a period of cost rationalization and funds restriction should be aimed to appropriate outcome measures corrected by both patient's risk factors and surgical-anaesthesiological case-mix. The development of a complete strategy for surgical pain management might run into two phases. The first phase, internal and mono-specialistic, should develop like the creation of an Acute Pain Team. The main processes are: focusing the problem (charge of the care), training, information, teaching methodology (timing, methods, drugs, techniques, etc.) and the audit (before and after changes). The main aims are the evaluation of the level of analgesia and pain relief or patient's satisfaction which are partial endpoints useful to demonstrate the improvement and the efficacy of the new pain management strategies. The second phase, multidisciplinary, is directed toward the creation of a Postoperative Evaluation Team. The main objective is to set up a collaborative clinical group able to identify the criteria for quality, efficacy and safety. The major purpose is the evaluation of major outcome measures: surgical outcome, morbidity, mortality and length of hospitalization. The improvement in the quality of postoperative pain treatment goes through a better organization and a progressive increase of the already available therapy. The achievement of the result and the quality projects depend on the interaction among staff members with different behaviours and settings. Internal teaching and training, continuous education for doctors and nurses, and external information, marketing and improvement of attractive capability of

  14. Lung Function and Organ Dysfunctions in 178 Patients Requiring Mechanical Ventilation During The 2009 Influenza A (H1N1) Pandemic

    PubMed Central

    2011-01-01

    Introduction Most cases of the 2009 influenza A (H1N1) infection are self-limited, but occasionally the disease evolves to a severe condition needing hospitalization. Here we describe the evolution of the respiratory compromise, ventilatory management and laboratory variables of patients with diffuse viral pneumonitis caused by pandemic 2009 influenza A (H1N1) admitted to the ICU. Method This was a multicenter, prospective inception cohort study including adult patients with acute respiratory failure requiring mechanical ventilation (MV) admitted to 20 ICUs in Argentina between June and September of 2009 during the influenza A (H1N1) pandemic. In a standard case-report form, we collected epidemiological characteristics, results of real-time reverse-transcriptase--polymerase-chain-reaction viral diagnostic tests, oxygenation variables, acid-base status, respiratory mechanics, ventilation management and laboratory tests. Variables were recorded on ICU admission and at days 3, 7 and 10. Results During the study period 178 patients with diffuse viral pneumonitis requiring MV were admitted. They were 44 ± 15 years of age, with Acute Physiology And Chronic Health Evaluation II (APACHE II) scores of 18 ± 7, and most frequent comorbidities were obesity (26%), previous respiratory disease (24%) and immunosuppression (16%). Non-invasive ventilation (NIV) was applied in 49 (28%) patients on admission, but 94% were later intubated. Acute respiratory distress syndrome (ARDS) was present throughout the entire ICU stay in the whole group (mean PaO2/FIO2 170 ± 25). Tidal-volumes used were 7.8 to 8.1 ml/kg (ideal body weight), plateau pressures always remained < 30 cmH2O, without differences between survivors and non-survivors; and mean positive end-expiratory pressure (PEEP) levels used were between 8 to 12 cm H2O. Rescue therapies, like recruitment maneuvers (8 to 35%), prone positioning (12 to 24%) and tracheal gas insufflation (3%) were frequently applied. At all time points

  15. Catastrophic antiphospholipid antibody syndrome presenting as acute vascular occlusion in a young female patient.

    PubMed

    Alonso, Joaquín Valle; Del Pozo, Francisco Javier Fonseca; Álvarez, Manuel Vaquero; Pedraza, Jorge; Aguayo, Miguel Angel; Sanchez, Almudena

    2016-10-10

    Acquired thrombotic and thromboembolic disorders may be presented initially with symptoms and signs of acute ischaemia or organ dysfunction that will lead many of these patients to seek care in the emergency department. We report a case of a 19-year-old female patient who developed catastrophic antiphospholipid syndrome (CAPS syndrome or Asherson syndrome) 6 weeks post stillbirth with an initial presentation of acute vascular occlusion. The patient was immediately operated and anticoagulated with significant improvement.

  16. Modification in CSF specific gravity in acutely decompensated cirrhosis and acute on chronic liver failure independent of encephalopathy, evidences for an early blood-CSF barrier dysfunction in cirrhosis.

    PubMed

    Weiss, Nicolas; Rosselli, Matteo; Mouri, Sarah; Galanaud, Damien; Puybasset, Louis; Agarwal, Banwari; Thabut, Dominique; Jalan, Rajiv

    2017-04-01

    Although hepatic encephalopathy (HE) on the background of acute on chronic liver failure (ACLF) is associated with high mortality rates, it is unknown whether this is due to increased blood-brain barrier permeability. Specific gravity of cerebrospinal fluid measured by CT is able to estimate blood-cerebrospinal fluid-barrier permeability. This study aimed to assess cerebrospinal fluid specific gravity in acutely decompensated cirrhosis and to compare it in patients with or without ACLF and with or without hepatic encephalopathy. We identified all the patients admitted for acute decompensation of cirrhosis who underwent a brain CT-scan. Those patients could present acute decompensation with or without ACLF. The presence of hepatic encephalopathy was noted. They were compared to a group of stable cirrhotic patients and healthy controls. Quantitative brain CT analysis used the Brainview software that gives the weight, the volume and the specific gravity of each determined brain regions. Results are given as median and interquartile ranges and as relative variation compared to the control/baseline group. 36 patients presented an acute decompensation of cirrhosis. Among them, 25 presented with ACLF and 11 without ACLF; 20 presented with hepatic encephalopathy grade ≥ 2. They were compared to 31 stable cirrhosis patients and 61 healthy controls. Cirrhotic patients had increased cerebrospinal fluid specific gravity (CSF-SG) compared to healthy controls (+0.4 %, p < 0.0001). Cirrhotic patients with ACLF have decreased CSF-SG as compared to cirrhotic patients without ACLF (-0.2 %, p = 0.0030) that remained higher than in healthy controls. The presence of hepatic encephalopathy did not modify CSF-SG (-0.09 %, p = 0.1757). Specific gravity did not differ between different brain regions according to the presence or absence of either ACLF or HE. In patients with acute decompensation of cirrhosis, and those with ACLF, CSF specific gravity is modified compared to

  17. Clinical significance of high c-MYC and low MYCBP2 expression and their association with Ikaros dysfunction in adult acute lymphoblastic leukemia.

    PubMed

    Ge, Zheng; Guo, Xing; Li, Jianyong; Hartman, Melanie; Kawasawa, Yuka Imamura; Dovat, Sinisa; Song, Chunhua

    2015-12-08

    Increased expression of c-MYC is observed in both Acute Myeloid Leukemia (AML) and T-cell Acute Lymphoblastic Leukemia (T-ALL). MYC binding protein 2 (MYCBP2) is a probable E3 ubiquitin ligase and its function in leukemia is unknown. IKZF1 deletion is associated with the development and poor outcome of ALL. Here, we observed significant high c-MYC expression and low MYCBP2 expression in adult ALL patients. Patients with high c-MYC expression and/or low MYCBP2 expression had higher WBC counts and a higher percentage of CD34+ or CD33+ cells, as well as splenomegaly, liver infiltration, higher BM blasts, and lower CR rate. Ikaros bound to the regulatory regions of c-MYC and MYCBP2, suppressed c-MYC and increased MYCBP2 expression in ALL cells. Expression of c-MYC mRNA was significantly higher in patients with IKZF1 deletion; conversely MYCBP2 mRNA expression was significantly lower in those patients. A CK2 inhibitor, which acts as an Ikaros activator, also suppressed c-MYC and increased MYCBP2 expression in an Ikaros (IKZF1) dependent manner in the ALL cells. In summary, our data indicated the correlation of high c-MYC expression, low MYCBP2 expression and high c-MYC plus low MYCBP2 expression with high-risk factors and proliferation markers in adult ALL patients. Our data also revealed an oncogenic role for an Ikaros/MYCBP2/c-MYC axis in adult ALL, providing a mechanism of target therapies that activate Ikaros in adult ALL.

  18. A single serving of blueberry (V. corymbosum) modulates peripheral arterial dysfunction induced by acute cigarette smoking in young volunteers: a randomized-controlled trial.

    PubMed

    Del Bo', Cristian; Porrini, Marisa; Fracassetti, Daniela; Campolo, Jonica; Klimis-Zacas, Dorothy; Riso, Patrizia

    2014-12-01

    Cigarette smoking causes oxidative stress, hypertension and endothelial dysfunction. Polyphenol-rich foods may prevent these conditions. We investigated the effect of a single serving of fresh-frozen blueberry intake on peripheral arterial function and arterial stiffness in young smokers. Sixteen male smokers were recruited for a 3-armed randomized-controlled study with the following experimental conditions: smoking treatment (one cigarette); blueberry treatment (300 g of blueberry) + smoking; control treatment (300 mL of water with sugar) + smoking. Each treatment was separated by one week of wash-out period. The blood pressure, heart rate, peripheral arterial function (reactive hyperemia and Framingham reactive hyperemia), and arterial stiffness (digital augmentation index, digital augmentation index normalized for a heart rate of 75 bpm) were measured before and 20 min after smoking with Endo-PAT2000. Smoking impaired the blood pressure, heart rate and peripheral arterial function, but did not affect the arterial stiffness. Blueberry consumption counteracted the impairment of the reactive hyperemia index induced by smoking (-4.4 ± 0.8% blueberry treatment vs. -22.0 ± 1.1% smoking treatment, p < 0.01) and Framingham reactive hyperemia (+28.3 ± 19.2% blueberry treatment vs. -42.8 ± 20.0% smoking treatment, p < 0.0001), and the increase of systolic blood pressure (+8.4 ± 0.02% blueberry treatment vs. +13.1 ± 0.02% smoking treatment, mmHg, p < 0.05) after cigarette smoking. No effect was observed for arterial stiffness and other vital signs. In conclusion, data obtained suggest a protective role of blueberry on reactive hyperemia, Framingham reactive hyperemia, and systolic blood pressure in subjects exposed to smoke of one cigarette. Future studies are necessary to elucidate the mechanisms involved.

  19. Elevated systemic elimination of cimetidine in rats with acute biliary obstruction: the role of renal organic cation transporter OCT2.

    PubMed

    Kurata, Tomohiko; Muraki, Yuichi; Mizutani, Hideki; Iwamoto, Takuya; Okuda, Masahiro

    2010-01-01

    Renal tubular secretion of cationic drugs is dominated by two classes of organic cation transporters, OCT2/SLC22A2 and MATE1/SLC47A1, localized to the basolateral and brush-border membranes of the renal tubular epithelial cells, respectively. However, little is known about the expression and function of these transporters in acute cholestasis. Systemic clearance of cimetidine was significantly higher in rats with bile duct ligation (BDL) for 24 hours than in sham-operated rats, with no significant changes in the volume of distribution between the groups. In addition, net tubular secretory clearance of cimetidine was significantly higher in the BDL rats compared with the sham rats, with no significant changes in the glomerular filtration rate. Moreover, the renal tissue-to-plasma concentration ratio of cimetidine was elevated in BDL rats, although the renal tissue-to-urine clearance ratio of cimetidine was not different between the two groups. The expression level of basolateral organic cation transporter rOCT2 protein in the kidney cortex was markedly higher in BDL rats than that in the sham rats, but that of H+/organic cation antiporter rMATE1 protein in the brush-border membranes was not significantly different between the two groups. These results demonstrate that the renal tubular secretion of cimetidine was increased by acute cholestasis, and this increase was attributable to elevated expression levels of rOCT2 but not of rMATE1 in the rat.

  20. Diastolic dysfunction in the critically ill patient.

    PubMed

    Suárez, J C; López, P; Mancebo, J; Zapata, L

    2016-11-01

    Left ventricular diastolic dysfunction is a common finding in critically ill patients. It is characterized by a progressive deterioration of the relaxation and the compliance of the left ventricle. Two-dimensional and Doppler echocardiography is a cornerstone in its diagnosis. Acute pulmonary edema associated with hypertensive crisis is the most frequent presentation of diastolic dysfunction critically ill patients. Myocardial ischemia, sepsis and weaning failure from mechanical ventilation also may be associated with diastolic dysfunction. The treatment is based on the reduction of pulmonary congestion and left ventricular filling pressures. Some studies have found a prognostic role of diastolic dysfunction in some diseases such as sepsis. The present review aims to analyze thoroughly the echocardiographic diagnosis and the most frequent scenarios in critically ill patients in whom diastolic dysfunction plays a key role.

  1. Reactive oxygen species produced by NADPH oxidase and mitochondrial dysfunction in lung after an acute exposure to Residual Oil Fly Ashes

    SciTech Connect

    Magnani, Natalia D.; Marchini, Timoteo; Vanasco, Virginia; Tasat, Deborah R.; Alvarez, Silvia; Evelson, Pablo

    2013-07-01

    Reactive O{sub 2} species production triggered by particulate matter (PM) exposure is able to initiate oxidative damage mechanisms, which are postulated as responsible for increased morbidity along with the aggravation of respiratory diseases. The aim of this work was to quantitatively analyse the major sources of reactive O{sub 2} species involved in lung O{sub 2} metabolism after an acute exposure to Residual Oil Fly Ashes (ROFAs). Mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight), and lung samples were analysed 1 h after instillation. Tissue O{sub 2} consumption and NADPH oxidase (Nox) activity were evaluated in tissue homogenates. Mitochondrial respiration, respiratory chain complexes activity, H{sub 2}O{sub 2} and ATP production rates, mitochondrial membrane potential and oxidative damage markers were assessed in isolated mitochondria. ROFA exposure was found to be associated with 61% increased tissue O{sub 2} consumption, a 30% increase in Nox activity, a 33% increased state 3 mitochondrial O{sub 2} consumption and a mitochondrial complex II activity increased by 25%. During mitochondrial active respiration, mitochondrial depolarization and a 53% decreased ATP production rate were observed. Neither changes in H{sub 2}O{sub 2} production rate, nor oxidative damage in isolated mitochondria were observed after the instillation. After an acute ROFA exposure, increased tissue O{sub 2} consumption may account for an augmented Nox activity, causing an increased O{sub 2}{sup ·−} production. The mitochondrial function modifications found may prevent oxidative damage within the organelle. These findings provide new insights to the understanding of the mechanisms involving reactive O{sub 2} species production in the lung triggered by ROFA exposure. - Highlights: • Exposure to ROFA alters the oxidative metabolism in mice lung. • The augmented Nox activity contributes to the high tissue O{sub 2} consumption. • Exposure to ROFA

  2. Management of Chronic Spinal Cord Dysfunction

    PubMed Central

    Abrams, Gary M.; Ganguly, Karunesh

    2015-01-01

    Purpose of Review: Both acute and chronic spinal cord disorders present multisystem management problems to the clinician. This article highlights key issues associated with chronic spinal cord dysfunction. Recent Findings: Advances in symptomatic management for chronic spinal cord dysfunction include use of botulinum toxin to manage detrusor hyperreflexia, pregabalin for management of neuropathic pain, and intensive locomotor training for improved walking ability in incomplete spinal cord injuries. Summary: The care of spinal cord dysfunction has advanced significantly over the past 2 decades. Management and treatment of neurologic and non-neurologic complications of chronic myelopathies ensure that each patient will be able to maximize their functional independence and quality of life. PMID:25651225

  3. Sexual dysfunction in diabetes.

    PubMed

    Tamás, Várkonyi; Kempler, Peter

    2014-01-01

    We aimed to summarize the etiology, clinical characteristics, diagnosis, and possible treatment options of sexual dysfunction in diabetic patients of both sexes. Details of dysfunction in diabetic women are less conclusive than in men due to the lack of standardized evaluation of sexual function in women. Male sexual dysfunction is a common complication of diabetes, including abnormalities of orgasmic/ejaculatory function and desire/libido in addition to penile erection. The prevalence of erectile dysfunction (ED) among diabetic men varies from 35% to 75%. Diabetes-induced ED has a multifactorial etiology including metabolic, neurologic, vascular, hormonal, and psychological components. ED should be regarded as the first sign of cardiovascular disease because it can be present before development of symptomatic coronary artery disease, as larger coronary vessels better tolerate the same amount of plaque compared to smaller penile arteries. The diagnosis of ED is based on validated questionnaires and determination of functional and organic abnormalities. First-, second- and third-line therapy may be applied. Phosphodiesterase-5 (PDE-5) inhibitor treatment from the first-line options leads to smooth muscle relaxation in the corpus cavernosum and enhancement in blood flow, resulting in erection during sexual stimulus. The use of PDE-5 inhibitors in the presence of oral nitrates is strictly contraindicated in diabetic men, as in nondiabetic subjects. All PDE-5 inhibitors have been evaluated for ED in diabetic patients with convincing efficacy data. Second-line therapy includes intracavernosal, trans- or intraurethral administration of vasoactive drugs or application of a vacuum device. Third-line therapies are the implantation of penile prosthesis and penile revascularization.

  4. Combination Targeted Therapy to Disrupt Aberrant Oncogenic Signaling and Reverse Epigenetic Dysfunction in IDH2- and TET2-Mutant Acute Myeloid Leukemia.

    PubMed

    Shih, Alan H; Meydan, Cem; Shank, Kaitlyn; Garrett-Bakelman, Francine E; Ward, Patrick S; Intlekofer, Andrew; Nazir, Abbas; Stein, Eytan; Knapp, Kristina; Glass, Jacob; Travins, Jeremy; Straley, Kim; Gliser, Camelia; Mason, Chris; Yen, Katharine; Thompson, Craig B; Melnick, Ari; Levine, Ross L

    2017-02-13

    Genomic studies in acute myeloid leukemias (AML) have identified mutations which drive altered DNA methylation, including TET2 and IDH2. Here we show that models of AMLs resulting from TET2 or IDH2 mutations combined with FLT3ITD mutations are sensitive to 5-Azacytidine or to the IDH2 inhibitor AG-221, respectively. 5-Azacytidine and AG-221 treatment induced an attenuation of aberrant DNA methylation and transcriptional output, and resulted in a reduction in leukemic blasts consistent with anti-leukemic activity. These therapeutic benefits were associated with restoration of leukemic cell differentiation, and the normalization of hematopoiesis was derived from mutant cells. By contrast, combining AG-221 or 5-Azacytidine with FLT3 inhibition resulted in a reduction in mutant allele burden, progressive recovery of normal hematopoiesis from non-mutant stem-progenitor cells, and reversal of dysregulated DNA methylation and transcriptional output. Together, our studies suggest combined targeting of signaling and epigenetic pathways can increase therapeutic response in AML.

  5. Resting thallium-201 myocardial perfusion patterns in patients with severe left ventricular dysfunction: differences between patients with primary cardiomyopathy, chronic coronary artery disease, or acute myocardial infarction

    SciTech Connect

    Iskandrian, A.S.; Hakki, A.H.; Kane, S.

    1986-04-01

    This study examined the value of resting thallium-201 imaging in differentiating patients with primary cardiomyopathy from those with ischemic cardiomyopathy. There were 15 patients with primary cardiomyopathy (group I); 20 with chronic CAD (group II); and 25 with acute Q wave myocardial infarction (group III). All patients had LVEF less than or equal to 35%. The thallium score was less than 50 (maximum 60) in one patient (7%) in group I, in 17 patients (85%) in group II, and in 25 patients (100%) in group III (p less than 0.0001, I vs II and III). The number of normal segments was 11.4 +/- 4.9 in group I, 6.9 +/- 2.9 in group II, and 7.0 +/- 2.2 in group III (p less than 0.0001, I vs II, III). Reversible defects were present in three patients in group II, three in group III, and none in group I. Abnormal right ventricular thallium uptake was observed in 27% of patients in group I, 25% in group II, and 40% in group III (p = NS). Abnormal lung thallium uptake was observed in 33% in group I, 20% in group II, and 20% in group III (p = NS). Thus, rest thallium imaging is useful in separating patients with primary cardiomyopathy from those with ischemic cardiomyopathy.

  6. Regulation of A-Kinase-Anchoring Protein 12 by Heat Shock Protein A12B to Prevent Ventricular Dysfunction Following Acute Myocardial Infarction in Diabetic Rats.

    PubMed

    Selvaraju, Vaithinathan; Suresh, Sumanth C; Thirunavukkarasu, Mahesh; Mannu, Jayakanthan; Foye, Jocelyn L C; Mathur, Premendu P; Palesty, J Alexander; Sanchez, Juan A; McFadden, David W; Maulik, Nilanjana

    2017-03-09

    We examined the effects of overexpressing HSPA12B on angiogenesis and myocardial function by intramyocardial administration of adenovirus encoding HSPA12B (Ad. HSPA12B) in a streptozotocin-induced diabetic rat subjected to myocardial infarction. Rats were divided randomly into six groups: control sham (CS) + Ad.LacZ, control myocardial infarction (CMI) + Ad.LacZ, control MI + Ad.HSPA12B, diabetic sham (DS) + Ad.LacZ, diabetic MI + Ad.LacZ and diabetic MI + Ad.HSPA12B. Following MI or sham surgery, the respective groups received either Ad.LacZ or Ad.HSPA12B via intramyocardial injections. We observed increased capillary and arteriolar density along with reduced fibrosis and preserved heart functions in DMI-AdHSPA12B compared to DMI-AdLacZ group. Western blot analysis demonstrated enhanced HSPA12B, vascular endothelial growth factor (VEGF), thioredoxin-1 (Trx-1) expression along with decreased expression of thioredoxin interacting protein (TXNIP) and A kinase anchoring protein 12 (AKAP12) in the DMI-AdHSPA12B compared to DMI-AdLacZ group. Our findings reveal that HSPA12B overexpression interacts with AKAP12 and downregulate TXNIP in diabetic rats following acute MI.

  7. Acute toxicity impacts of Euphorbia hirta L extract on behavior, organs body weight index and histopathology of organs of the mice and Artemia salina

    PubMed Central

    Rajeh, Mohammad Abu Basma; Kwan, Yuet Ping; Zakaria, Zuraini; Latha, Lachimanan Yoga; Jothy, Subramanion L.; Sasidharan, Sreenivasan

    2012-01-01

    Background: The methanol extract of Euphorbia hirta L (Euphorbiaceae), which is used in traditional medicines, was tested for in vivo toxicity. Materials and Methods: In vivo brine shrimp lethality assay and oral acute toxicity study at single high dose of 5000 mg/kg and observation for 14 days in mice were used to study the toxic effect of E. hirta. Results: Brine shrimp lethality assay was used to calculate the median lethal concentration (LC50) of E. hirta (for leaves, stems, flowers and roots) methanolic extracts at concentrations from 100 to 0.07 mg/ml. The LC50 values of 1.589, 1.420, 0.206 and 0.0827 mg/ml were obtained for stems, leaves, flowers and roots, respectively. Potassium dichromate (the positive control) had LC50 value of 0.00758 mg/ml. The acute oral toxicity study of the leaf extract resulted in one third mortality and mild behavioral changes among the treated mice. No significant statistical differences found between body weight, relative (%) and absolute (g) organ weights of treated and untreated groups (P> 0.05). Gross and microscopic examination of the vital organ tissues revealed no differences between control and treated mice. All the tissues appeared normal. Conclusions: E. hirta leaves methanol extract has exhibited mild toxic effects in mice. PMID:22923956

  8. Hepatitis E virus quasispecies and the outcome of acute hepatitis E in solid-organ transplant patients.

    PubMed

    Lhomme, Sebastien; Abravanel, Florence; Dubois, Martine; Sandres-Saune, Karine; Rostaing, Lionel; Kamar, Nassim; Izopet, Jacques

    2012-09-01

    Hepatitis E virus (HEV) infections are responsible for chronic hepatitis in immunocompromised patients, and this can evolve to cirrhosis. Like all RNA viruses, HEV exists as a mixture of heterogeneous viruses defining quasispecies. The relationship between the genetic heterogeneity described as a quasispecies, cytokine secretion, and the outcome of acute hepatitis in immunocompromised patients remains to be elucidated. We cloned and sequenced the region encoding the M and P capsid domains of HEV from eight solid-organ transplant (SOT) patients with acute HEV infection who subsequently cleared the virus and from eight SOT patients whose infection became chronic. We analyzed the cytokines and chemokines in the sera of these SOT patients by multianalyte profiling. The nucleotide sequence entropy and genetic distances were greater in patients whose infections became chronic. A lower K(a)/K(s) ratio was associated with the persistence of HEV. The patients who developed chronic infection had lower serum concentrations of interleukin-1 (IL-1) receptor antagonist and soluble IL-2 receptor. Increased concentrations of the chemokines implicated in leukocyte recruitment to the liver were associated with persistent infection. Those patients with chronic HEV infection and progressing liver fibrosis had less quasispecies diversification during the first year than patients without liver fibrosis progression. Great quasispecies heterogeneity, a weak inflammatory response, and high serum concentrations of the chemokines involved in leukocyte recruitment to the liver in the acute phase were associated with persistent HEV infection. Slow quasispecies diversification during the first year was associated with rapidly developing liver fibrosis.

  9. Family dysfunction

    PubMed Central

    Hayaki, Chie; Anno, Kozo; Shibata, Mao; Iwaki, Rie; Kawata, Hiroshi; Sudo, Nobuyuki; Hosoi, Masako

    2016-01-01

    Abstract Previous studies have shown differences in the psychosocial factors related to chronic localized pain (CLP) and chronic widespread pain (CWP). However, no studies have done an evaluation of differences between CLP and CWP from the viewpoint of family functioning. We did a cross-sectional study in a tertiary care setting to investigate possible differences in the relation of CWP and CLP to family functioning. Patients with CLP (N = 126) or CWP (N = 75) were assessed for family functioning by the Family Assessment Device (FAD) and a comparison was done. Logistic regression analysis was used to estimate associations of family functioning subscales with pain status (CWP vs CLP), controlling for demographic variables, pain variables; pain duration, pain ratings, pain disability, and psychological factors; depression, anxiety, and catastrophizing. The odds ratios (ORs) for the presence of CWP were calculated. Compared to patients with CLP, patients with CWP showed a lower functional status for Roles and Affective Involvement. The ORs for CWP were significantly higher in lower functioning Roles (OR: 2.38, 95% CI: 1.21–4.65) and Affective Involvement (OR: 2.86, 95% CI: 1.56–5.24) after adjusting for demographic variables. The significant association of CWP to Roles and Affective Involvement remained after controlling for the pain variables and psychological factors. This study shows that the families of patients with CWP have poorer family functioning than those with CLP. Our findings suggest that early identification and interventions for the family dysfunction of chronic pain patients are important to the treatment and prevention of CWP. PMID:27930535

  10. Human Alpha-1-Antitrypsin (hAAT) therapy reduces renal dysfunction and acute tubular necrosis in a murine model of bilateral kidney ischemia-reperfusion injury

    PubMed Central

    Maicas, Nuria; van der Vlag, Johan; Bublitz, Janin; Florquin, Sandrine; Bakker-van Bebber, Marinka; Dinarello, Charles A.; Verweij, Vivienne; Masereeuw, Roos; Joosten, Leo A.

    2017-01-01

    Several lines of evidence have demonstrated the anti-inflammatory and cytoprotective effects of alpha-1-antitrypsin (AAT), the major serum serine protease inhibitor. The aim of the present study was to investigate the effects of human AAT (hAAT) monotherapy during the early and recovery phase of ischemia-induced acute kidney injury. Mild renal ischemia-reperfusion (I/R) injury was induced in male C57Bl/6 mice by bilateral clamping of the renal artery and vein for 20 min. hAAT (80 mg/kg, Prolastin®) was administered daily intraperitoneally (i.p.) from day -1 until day 7 after surgery. Control animals received the same amount of human serum albumin (hAlb). Plasma, urine and kidneys were collected at 2h, 1, 2, 3, 8 and 15 days after reperfusion for histological and biochemical analysis. hAAT partially preserved renal function and tubular integrity after induction of bilateral kidney I/R injury, which was accompanied with reduced renal influx of macrophages and a significant decrease of neutrophil gelatinase-associated lipocalin (NGAL) protein levels in urine and plasma. During the recovery phase, hAAT significantly decreased kidney injury molecule-1 (KIM-1) protein levels in urine but showed no significant effect on renal fibrosis. Although the observed effect size of hAAT administration was limited and therefore the clinical relevance of our findings should be evaluated carefully, these data support the potential of this natural protein to ameliorate ischemic and inflammatory conditions. PMID:28235038

  11. Acute pancreatitis: The stress factor

    PubMed Central

    Binker, Marcelo G; Cosen-Binker, Laura I

    2014-01-01

    Acute pancreatitis is an inflammatory disorder of the pancreas that may cause life-threatening complications. Etiologies of pancreatitis vary, with gallstones accounting for the majority of all cases, followed by alcohol. Other causes of pancreatitis include trauma, ischemia, mechanical obstruction, infections, autoimmune, hereditary, and drugs. The main events occurring in the pancreatic acinar cell that initiate and propagate acute pancreatitis include inhibition of secretion, intracellular activation of proteases, and generation of inflammatory mediators. Small cytokines known as chemokines are released from damaged pancreatic cells and attract inflammatory cells, whose systemic action ultimately determined the severity of the disease. Indeed, severe forms of pancreatitis may result in systemic inflammatory response syndrome and multiorgan dysfunction syndrome, characterized by a progressive physiologic failure of several interdependent organ systems. Stress occurs when homeostasis is threatened, and stressors can include physical or mental forces, or combinations of both. Depending on the timing and duration, stress can result in beneficial or harmful consequences. While it is well established that a previous acute-short-term stress decreases the severity of experimentally-induced pancreatitis, the worsening effects of chronic stress on the exocrine pancreas have received relatively little attention. This review will focus on the influence of both prior acute-short-term and chronic stress in acute pancreatitis. PMID:24914340

  12. [Mathematical analysis of complicated course of acute surgical diseases of abdominal cavity organs].

    PubMed

    Vozniuk, S M; Pol'ovyĭ, V P; Sydorchuk, R I; Palianytsia, A S

    2013-03-01

    In this paper we analyze the results of diagnosis and treatment of 130 patients with acute surgical diseases of the abdominal cavity, complicated by peritonitis. We proposed the method of estimating the severity of the patients using a coefficient of status severity (C(SS)), developed a scale for prediction of complicated outcomes of acute surgical pathology of the abdominal cavity and abdominal sepsis, which is adapted to the working conditions of local clinics. Using the C(SS) and the scale prediction, allowed timely identification of patients' risk group with possible complicated course, assign adequate treatment, reduce postoperative complications by 5%, relaparotomies by 4.4%, decrease postoperative mortality by 3.9%.

  13. World Health Organization Grade II Oligodendroglioma Occurring after Successful Treatment for Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Yoon, Sang-In; Park, Dong-Hyuk; Kang, Shin-Hyuk; Park, Jung-Yul; Chung, Yong-Gu

    2016-01-01

    When treating childhood acute lymphoblastic leukemia (ALL), secondary neoplasms are a significant long term problem. Radiation is generally accepted to be a major cause of the development of secondary neoplasms. Following treatment for ALL, a variety of secondary tumors, including brain tumors, hematologic malignancies, sarcomas, thyroid cancers, and skin cancers have been reported. However, oligodendroglioma as a secondary neoplasm is extremely rare. Herein we present a case of secondary oligodendroglioma occurring 13 years after the end of ALL treatment. PMID:27867928

  14. Acute and chronic toxicity of sodium sulfate to four freshwater organisms in water-only exposures

    USGS Publications Warehouse

    Wang, Ning; Consbrock, Rebecca A.; Ingersoll, Christopher G.; Hardesty, Douglas K.; Brumbaugh, William G.; Hammer, Edward J.; Bauer, Candice R.; Mount, David R.

    2016-01-01

    The acute and chronic toxicity of sulfate (tested as sodium sulfate) was determined in diluted well water (hardness of 100 mg/L and pH 8.2) with a cladoceran (Ceriodaphnia dubia; 2-d and 7-d exposures), a midge (Chironomus dilutus; 4-d and 41-d exposures), a unionid mussel (pink mucket, Lampsilis abrupta; 4-d and 28-d exposures), and a fish (fathead minnow, Pimephales promelas; 4-d and 34-d exposures). Among the 4 species, the cladoceran and mussel were acutely more sensitive to sulfate than the midge and fathead minnow, whereas the fathead minnow was chronically more sensitive than the other 3 species. Acute-to-chronic ratios ranged from 2.34 to 5.68 for the 3 invertebrates but were as high as 12.69 for the fish. The fathead minnow was highly sensitive to sulfate during the transitional period from embryo development to hatching in the diluted well water, and thus, additional short-term (7- to 14-d) sulfate toxicity tests were conducted starting with embryonic fathead minnow in test waters with different ionic compositions at a water hardness of 100 mg/L. Increasing chloride in test water from 10 mg Cl/L to 25 mg Cl/L did not influence sulfate toxicity to the fish, whereas increasing potassium in test water from 1mg K/L to 3mg K/L substantially reduced the toxicity of sulfate. The results indicate that both acute and chronic sulfate toxicity data, and the influence of potassium on sulfate toxicity to fish embryos, need to be considered when environmental guidance values for sulfate are developed or refined.

  15. Acute and chronic toxicity of sodium sulfate to four freshwater organisms in water-only exposures.

    PubMed

    Wang, Ning; Dorman, Rebecca A; Ingersoll, Christopher G; Hardesty, Doug K; Brumbaugh, William G; Hammer, Edward J; Bauer, Candice R; Mount, David R

    2016-01-01

    The acute and chronic toxicity of sulfate (tested as sodium sulfate) was determined in diluted well water (hardness of 100 mg/L and pH 8.2) with a cladoceran (Ceriodaphnia dubia; 2-d and 7-d exposures), a midge (Chironomus dilutus; 4-d and 41-d exposures), a unionid mussel (pink mucket, Lampsilis abrupta; 4-d and 28-d exposures), and a fish (fathead minnow, Pimephales promelas; 4-d and 34-d exposures). Among the 4 species, the cladoceran and mussel were acutely more sensitive to sulfate than the midge and fathead minnow, whereas the fathead minnow was chronically more sensitive than the other 3 species. Acute-to-chronic ratios ranged from 2.34 to 5.68 for the 3 invertebrates but were as high as 12.69 for the fish. The fathead minnow was highly sensitive to sulfate during the transitional period from embryo development to hatching in the diluted well water, and thus, additional short-term (7- to 14-d) sulfate toxicity tests were conducted starting with embryonic fathead minnow in test waters with different ionic compositions at a water hardness of 100 mg/L. Increasing chloride in test water from 10 mg Cl/L to 25 mg Cl/L did not influence sulfate toxicity to the fish, whereas increasing potassium in test water from 1 mg K/L to 3 mg K/L substantially reduced the toxicity of sulfate. The results indicate that both acute and chronic sulfate toxicity data, and the influence of potassium on sulfate toxicity to fish embryos, need to be considered when environmental guidance values for sulfate are developed or refined.

  16. Three dimensional quantitative structure-toxicity relationship modeling and prediction of acute toxicity for organic contaminants to algae.

    PubMed

    Jin, Xiangqin; Jin, Minghao; Sheng, Lianxi

    2014-08-01

    Although numerous chemicals have been identified to have significant toxicological effect on aquatic organisms, there is still lack of a reliable, high-throughput approach to evaluate, screen and monitor the presence of organic contaminants in aquatic system. In the current study, we proposed a synthetic pipeline to automatically model and predict the acute toxicity of chemicals to algae. In the procedure, a new alignment-free three dimensional (3D) structure characterization method was described and, with this method, several 3D-quantitative structure-toxicity relationship (3D-QSTR) models were developed, from which two were found to exhibit strong internal fitting ability and high external predictive power. The best model was established by Gaussian process (GP), which was further employed to perform extrapolation on a random compound library consisting of 1014 virtually generated substituted benzenes. It was found that (i) substitution number can only exert slight influence on chemical׳s toxicity, but low-substituted benzenes seem to have higher toxicity than those of high-substituted entities, and (ii) benzenes substituted by nitro group and halogens exhibit high acute toxicity as compared to other substituents such as methyl and carboxyl groups. Subsequently, several promising candidates suggested by computational prediction were assayed by using a standard algal growth inhibition test. Consequently, four substituted benzenes, namely 2,3-dinitrophenol, 2-chloro-4-nitroaniline, 1,2,3-trinitrobenzene and 3-bromophenol, were determined to have high acute toxicity to Scenedesmus obliquus, with their EC50 values of 2.5±0.8, 10.5±2.1, 1.4±0.2 and 42.7±5.4μmol/L, respectively.

  17. Early liver transplantation for patients with acute alcoholic hepatitis: public views and the effects on organ donation.

    PubMed

    Stroh, G; Rosell, T; Dong, F; Forster, J

    2015-06-01

    Patients with severe acute alcoholic hepatitis may not survive to fulfill the standard 6 months of abstinence and counseling prior to transplantation. A prospective study demonstrated that early liver transplantation in such patients improved 2 year survival from 23% to 71% and only 3 of 26 patients returned to drinking after 1140 days; graft function was unaffected. Nonetheless, this treatment protocol may raise public concerns and affect organ donation rates. A total of 503 participants took a survey made available at an online crowdsourcing marketplace. The survey measured attitudes on liver transplantation generally and early transplantation for this patient population, in addition to measuring responses to nine vignettes describing fictional candidates. The majority of respondents (81.5%, n = 410) was at least neutral toward early transplantation for these patients; only a minority (26.3%) indicated that transplantation in any vignette would make them hesitant to donate their organs. Middle-aged patients with good social support and financial stability were viewed most favorably (p < 0.001). Age was considered the most important selection factor and financial stability the least important factor (each p < 0.001). Results indicate early transplantation for carefully selected patients with acute alcoholic hepatitis may not be as controversial to the public as previously thought.

  18. The relationship between depression and erectile dysfunction.

    PubMed

    Seidman, S N; Roose, S P

    2000-06-01

    Normal sexual function is a biopsychosocial process; sexual dysfunction almost always has organic and psychologic components, and it requires multidisciplinary, goal-directed evaluation and treatment. Factors such as aging, declining testosterone levels, medical illness, certain medications, and comorbid depressive illness can contribute to sexual dysfunction. Erectile dysfunction (ED) is the most common male sexual dysfunction encountered in the clinical setting. Comorbidity between ED and depressive illness is high, but the causal relationship is unclear, and likely bidirectional. In this article, we review the existing literature on the relationship between depression and ED.

  19. Effect of sinusoidal modulated currents and acute hypoxia on corticosterone content and activity of certain dehydrogenases in tissues of different rat organs during hypokinesia

    NASA Technical Reports Server (NTRS)

    Melik-Aslanova, L. L.; Frenkel, I. D.

    1980-01-01

    The state of hypokinesia in rats was reproduced by keeping them for 30 days in special box cages that restricted their mobility in all directions. Results show the resistance to acute hypoxic hypoxia is increased. This is linked to the considerable rise in the reduced level of corticosterone in different organs and the succinate dehydrogenase activity in the liver and brain. The letter indicated the primary oxidation of succinate, which has great importance in the adaptation of the oxidative metabolism to acute oxygen insufficiency. The use of sinusoidal modulated currents in the period of hypokinesia promotes normalization of the indices for resistance of the rats to acute hypoxia.

  20. Renal dysfunction and coronary disease: a high-risk combination.

    PubMed

    Schiele, Francois

    2009-01-01

    Chronic kidney dysfunction is recognized as a risk factor for atherosclerosis and complicates strategies and treatment. Therefore, it is important for cardiologists not only to detect and measure potential kidney dysfunction, but also to know the mechanisms by which the heart and kidney interact, and recognize that in cases of acute coronary syndrome, the presence of renal dysfunction increases the risk of death. The detection and classification of kidney dysfunction into 5 stages is based on the estimated glomerular filtration rate (GFR). The presence of hypertension, endothelial dysfunction, dyslipidemia, inflammation, activation of the renin-angiotensin system and specific calcifications are the main mechanisms by which renal dysfunction can induce or compound cardiovascular disease. The magnitude of renal dysfunction is related to the cardiovascular risk; a linear relation links the extent of GFR decrease and the risk of cardiovascular events. Renal dysfunction and acute coronary syndromes are a dangerous combination: more common comorbidities, more frequent contraindications for effective drugs and higher numbers of drug-related adverse events such as bleeding partially explain the higher mortality in patients with renal dysfunction. In addition, despite higher risk, patients with renal dysfunction often receive fewer guideline-recommended treatments even in the absence of contraindications. Renal dysfunction induces and promotes atherosclerosis by various pathophysiologic pathways and is associated with other cardiovascular risk factors and underuse of appropriate therapy. Therefore, the assessment of renal function is an important step in the risk evaluation of patients with coronary artery disease.

  1. Relevance of stroke code, stroke unit and stroke networks in organization of acute stroke care--the Madrid acute stroke care program.

    PubMed

    Alonso de Leciñana-Cases, María; Gil-Núñez, Antonio; Díez-Tejedor, Exuperio

    2009-01-01

    Stroke is a neurological emergency. The early administration of specific treatment improves the prognosis of the patients. Emergency care systems with early warning for the hospital regarding patients who are candidates for this treatment (stroke code) increases the number of patients treated. Currently, reperfusion via thrombolysis for ischemic stroke and attention in stroke units are the bases of treatment. Healthcare professionals and health provision authorities need to work together to organize systems that ensure continuous quality care for the patients during the whole process of their disease. To implement this, there needs to be an appropriate analysis of the requirements and resources with the objective of their adjustment for efficient use. It is necessary to provide adequate information and continuous training for all professionals who are involved in stroke care, including primary care physicians, extrahospital emergency teams and all physicians involved in the care of stroke patients within the hospital. The neurologist has the function of coordinating the protocols of intrahospital care. These organizational plans should also take into account the process beyond the acute phase, to ensure the appropriate application of measures of secondary prevention, rehabilitation, and chronic care of the patients that remain in a dependent state. We describe here the stroke care program in the Community of Madrid (Spain).

  2. Acute toxicity of cypermethrin to the non target organism Hyalella curvispina.

    PubMed

    Mugni, Hernán; Paracampo, Ariel; Marrochi, Natalia; Bonetto, Carlos

    2013-01-01

    The acute toxicity of cypermethrin to the amphipod Hyalella curvispina was evaluated by means of a toxicity test under laboratory conditions. Cypermethrin is one of the most widely used insecticides in Argentina. H. curvispina is a widely distributed and commonly abundant component of the invertebrate assemblages in shallow waters of southern South America. The experiments were repeated three times. The mean 48-h LC(50) value for H. curvispina was estimated at 0.066μg/l. H. curvispina represents a good model for exotoxicological risk assessment.

  3. Pathophysiology of ischaemic acute kidney injury.

    PubMed

    Kanagasundaram, Nigel Suren

    2015-03-01

    Acute kidney injury is common, dangerous and costly, affecting around one in five patients emergency admissions to hospital. Although survival decreases as disease worsens, it is now apparent that even modest degrees of dysfunction are not only associated with higher mortality but are an independent risk factor for death. This review focuses on the pathophysiology of acute kidney injury secondary to ischaemia - its commonest aetiology. The haemodynamic disturbances, endothelial injury, epithelial cell injury and immunological mechanisms underpinning its initiation and extension will be discussed along with the considerable and complex interplay between these factors that lead to an intense, pro-inflammatory state. Mechanisms of tubular recovery will be discussed but also the pathophysiology of abnormal repair with its direct consequences for long-term renal function. Finally, the concept of 'organ cross-talk' will be introduced as a potential explanation for the higher mortality observed with acute kidney injury that might be deemed modest in conventional biochemical terms.

  4. Renal allograft eosinophilia: An unusual presentation of sudden graft dysfunction

    PubMed Central

    Yuvaraj, A.; Ghosh, S.; Abraham, G.; Koshy, P.

    2017-01-01

    We present a case of sudden allograft dysfunction 11 months after renal transplantation which presented as severe peripheral and allograft eosinophilia and was managed as a case of an acute cellular rejection with significant interstitial graft eosinophilic infiltration. Patient had partial response to antirejection therapy and eventually ended up in a chronic allograft dysfunction. PMID:28356665

  5. New insights into environmental enteric dysfunction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Environmental enteric dysfunction (EED) has been recognised as an important contributing factor to physical and cognitive stunting, poor response to oral vaccines, limited resilience to acute infections and ultimately global childhood mortality. The aetiology of EED remains poorly defined but the ep...

  6. Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease

    PubMed Central

    Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

    2011-01-01

    Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called “pelvic organ” dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and “prokinetic” drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life. PMID:21918729

  7. Acute kidney injury caused by zonisamide-induced hypersensitivity syndrome.

    PubMed

    Fujita, Yoshiro; Hasegawa, Midori; Nabeshima, Kuihiro; Tomita, Makoto; Murakami, Kazutaka; Nakai, Shigeru; Yamakita, Takashi; Matsunaga, Kayoko

    2010-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a severe adverse drug reaction affecting multiple organs caused by drug treatment. The current report describes a man who was prescribed zonisamide for epilepsy and subsequently developed widespread skin rash, acute kidney injury, high-grade fever, eosinophilia, liver dysfunction, lymphadenopathy and an increase in antihuman herpesvirus-6 immunoglobulin G titer. Hypersensitivity to zonisamide was confirmed by the skin patch test. Based on these findings, the patient was diagnosed with DRESS/DIHS caused by zonisamide. This is the first report of acute kidney injury due to zonisamide-induced DRESS/DIHS.

  8. Kinetic and organ-specific patterns of cytokine expression in acute graft-versus-host disease.

    PubMed

    Baker, K S; Allen, R D; Roths, J B; Sidman, C L

    1995-04-01

    Although many cytokines have been previously implicated in graft-versus-host disease (GVHD), no study to date has comprehensively evaluated their expression over time or in different tissues affected by GVHD. Using a semi-quantitative reverse transcriptase-PCR technique and a murine model of acute GVHD, we have evaluated the expression levels of mRNA for a wide range of cytokines in spleen, gut and liver tissues at weekly intervals after bone marrow transfer. The earliest cytokine responses seen were increases in IL-2, IL-10, IFN-gamma, MIP-1 alpha and TNF-alpha in the spleen, suggesting a primarily Th1 pathway. Other cytokines (IL-1 alpha, IL-10 and MIP-1 alpha) were persistently elevated in GVHD mice, but were variable depending on the tissue. These data demonstrate that a wide range of cytokines are involved in the GVHD response and that their kinetic pattern of expression is different in various affected tissues.

  9. Spautin-1 Ameliorates Acute Pancreatitis via Inhibiting Impaired Autophagy and Alleviating Calcium Overload

    PubMed Central

    Xiao, Juan; Feng, Xueping; Huang, Xiao-Ying; Huang, Zhongshi; Huang, Yanqiang; Li, Chaogan; Li, Genliang; Nong, Song; Wu, Ruoshi; Huang, Yongzhi; Long, Xi-Dai

    2016-01-01

    Acute pancreatitis is characterized by zymogen preactivation. Severe inflammation caused by zymogen activation can eventually lead to multiple organ dysfunctions which contribute to the high mortality rate of severe acute pancreatitis. However, there is no specific treatment available for acute pancreatitis therapy. Here, we show that spautin-1, which effectively inhibits autophagy flux, ameliorated the pathogenesis of acute pancreatitis induced by cerulein or L-arginine. CaMKII phosphorylation due to cytosolic calcium overload was revealed in this paper. It was also demonstrated that autophagic protein aggregates degradation blockade accompanied by impaired autophagy correlated positively with intra-acinar cell digestive aymogen activation stimulated by cerulein or L-arginine. The role of spautin-1 in ameliorating acute pancreatitis was shown here to be associated with impaired autophagy inhibition and Ca2+ overload alleviation. We provide a promising therapy for acute pancreatitis through targeting both impaired autophagy and increased cytosolic calcium. PMID:27579473

  10. Early molecular diagnosis of acute Chagas disease after transplantation with organs from Trypanosoma cruzi-infected donors.

    PubMed

    Cura, C I; Lattes, R; Nagel, C; Gimenez, M J; Blanes, M; Calabuig, E; Iranzo, A; Barcan, L A; Anders, M; Schijman, A G

    2013-12-01

    Organ transplantation (TX) is a novel transmission modality of Chagas disease. The results of molecular diagnosis and characterization of Trypanosoma cruzi acute infection in naïve TX recipients transplanted with organs from infected deceased donors are reported. Peripheral blood and cerebrospinal fluid samples from the TX recipients of organs from infected donors were prospectively and sequentially studied for detection of T. cruzi by means of kinetoplastid DNA polymerase chain reaction (kDNA-PCR). In positive blood samples, a PCR algorithm for identification of T. cruzi Discrete Typing Units (DTUs) and quantitative real-time PCR (qPCR) to quantify parasitic loads were performed. Minicircle signatures of T. cruzi infecting populations were also analyzed using restriction fragment length polymorphism (RFLP)-PCR. Eight seronegative TX recipients from four infected donors were studied. In five, the infection was detected at 68.4 days post-TX (36-98 days). In one case, it was transmitted to two of three TX recipients. The comparison of the minicircle signatures revealed nearly identical RFLP-PCR profiles, confirming a common source of infection. The five cases were infected by DTU TcV. This report reveals the relevance of systematic monitoring of TX recipients using PCR strategies in order to provide an early diagnosis allowing timely anti-trypanosomal treatment.

  11. [Clinical diagnosis of HIV infection in patients with acute surgical diseases of the abdominal cavity organs and pulmonary tuberculosis].

    PubMed

    Nguen, V Kh; Stroganov, P V; Geshelin, S A

    2011-09-01

    The results of treatment of 81 patients, suffering tuberculosis and operated in emergency for an acute surgical diseases of the abdominal cavity organs, are adduced, in 29 of them--nonspecific diseases of nontuberculosis genesis were diagnosed. In 52 patients the indication for emergency operation performance were complications of abdominal tuberculosis (perforation of the tuberculosis ulcers of small intestine--in 37, the tuberculosis mesadenitis--in 15), of them in 34--pulmonary tuberculosis was in inactive phase, that's why the HIV presence was supposed. In 26 patients the diagnosis was confirmed, basing on serologic analysis data. The presence of intraabdominal catastrophe, caused by abdominal tuberculosis complications on inactive pulmonary tuberculosis background witnesses with 85.3% probability the HIV-infectioning of the patient.

  12. Mitochondrial dysfunction in autism.

    PubMed

    Legido, Agustín; Jethva, Reena; Goldenthal, Michael J

    2013-09-01

    Using data of the current prevalence of autism as 200:10,000 and a 1:2000 incidence of definite mitochondrial (mt) disease, if there was no linkage of autism spectrum disorder (ASD) and mt disease, it would be expected that 1 in 110 subjects with mt disease would have ASD and 1 in 2000 individuals with ASD would have mt disease. The co-occurrence of autism and mt disease is much higher than these figures, suggesting a possible pathogenetic relationship. Such hypothesis was initially suggested by the presence of biochemical markers of abnormal mt metabolic function in patients with ASD, including elevation of lactate, pyruvate, or alanine levels in blood, cerebrospinal fluid, or brain; carnitine level in plasma; and level of organic acids in urine, and by demonstrating impaired mt fatty acid β-oxidation. More recently, mtDNA genetic mutations or deletions or mutations of nuclear genes regulating mt function have been associated with ASD in patients or in neuropathologic studies on the brains of patients with autism. In addition, the presence of dysfunction of the complexes of the mt respiratory chain or electron transport chain, indicating abnormal oxidative phosphorylation, has been reported in patients with ASD and in the autopsy samples of brains. Possible pathogenetic mechanisms linking mt dysfunction and ASD include mt activation of the immune system, abnormal mt Ca(2+) handling, and mt-induced oxidative stress. Genetic and epigenetic regulation of brain development may also be disrupted by mt dysfunction, including mt-induced oxidative stress. The role of the purinergic system linking mt dysfunction and ASD is currently under investigation. In summary, there is genetic and biochemical evidence for a mitochondria (mt) role in the pathogenesis of ASD in a subset of children. To determine the prevalence and type of genetic and biochemical mt defects in ASD, there is a need for further research using the latest genetic technology such as next

  13. The prolonged gastrointestinal syndrome in rhesus macaques: the relationship between gastrointestinal, hematopoietic, and delayed multi-organ sequelae following acute, potentially lethal, partial-body irradiation.

    PubMed

    MacVittie, Thomas J; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M

    2012-10-01

    The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min(-1) to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for

  14. Golgi tendon organ reflex inhibition following manually applied acute static stretching.

    PubMed

    Miller, Kevin C; Burne, John A

    2014-01-01

    Golgi tendon organ disinhibition may contribute to exercise-associated muscle cramp (henceforth referred to as "cramps") genesis. Static stretching pre-exercise is prescribed to prevent cramps based on the assumption golgi tendon organ inhibition remains elevated post-stretching. We determined whether stretching increased gastrocnemius golgi tendon organ inhibition and, if so, the time course of this inhibition post-stretching. Twelve participants' dominant limb medial gastrocnemius inhibition was measured before, and at 1, 5, 10, 15 and 30 min after investigators applied three, 1-min duration stretches. Participants maintained voluntary contraction intensities of 5% of their maximum while the Achilles tendon was stimulated transcutaneously 50 times. Five-hundred millisecond epochs of raw electromyographic activity were band-pass filtered, full-wave rectified and averaged. An algorithm identified inhibitory points and calculated the area, maximum and duration of inhibition. Area of inhibition (F1,14 = 1.5, P = 0.25), maximum inhibition (F1,14 = 0.2, P = 0.72) and duration of inhibition (F1,14 = 1.5, P = 0.24) were unaffected by static stretching over the 30-min post-stretching period. If pre-stretching does prevent fatigue-induced cramping, the mechanism is unlikely to involve the autoinhibition produced by the golgi tendon organ reflex. Further empirical research is needed to validate the proposed link between static stretching and cramping and then to investigate alternative mechanisms.

  15. Guillain-Barré Syndrome Presenting with Sinus Node Dysfunction and Refractory Shock

    PubMed Central

    Ha, Le Dung; Abbas, Farrukh; Rao, Mohan

    2017-01-01

    Patient: Male, 76 Final Diagnosis: Guillain-Barré syndrome Symptoms: Bradycardia • refractory hypotension Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Unusual clinical course Background: Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyneuropathy that is usually associated with preceding respiratory or gastrointestinal infection and has the hallmark manifestation of ascending flaccid paralysis. We report an atypical presentation of GBS. Case Report: A 76-year-old male presented with acute onset of diaphoresis and altered mental status. He subsequently developed severe bradycardia and refractory hypotension, which initially responded to dopamine infusion. A temporary pacemaker wire was placed to stabilize the heart rate but hypotension persisted. Acute autonomic dysfunction was suspected. Head and chest imaging was unrevealing. Lumbar puncture revealed albuminocytologic dissociation that was consistent with a diagnosis of GBS. Hospital course was complicated with acute kidney injury and metabolic acidosis. Plasmapharesis was initiated. The patient eventually died of multi-organ failure. Conclusions: Autonomic dysfunction is a known but rare presentation of GBS. In patients presenting with refractory bradycardia and hypotension, GBS should be considered in the differential diagnosis. PMID:28283677

  16. Acute toxicity of anionic and non-ionic surfactants to aquatic organisms.

    PubMed

    Lechuga, M; Fernández-Serrano, M; Jurado, E; Núñez-Olea, J; Ríos, F

    2016-03-01

    The environmental risk of surfactants requires toxicity measurements. As different test organisms have different sensitivity to the toxics, it is necessary to establish the most appropriate organism to classify the surfactant as very toxic, toxic, harmful or safe, in order to establish the maximum permissible concentrations in aquatic ecosystems. We have determined the toxicity values of various anionic surfactants ether carboxylic derivatives using four test organisms: the freshwater crustacean Daphnia magna, the luminescent bacterium Vibrio fischeri, the microalgae Selenastrum capricornutum (freshwater algae) and Phaeodactylum tricornutum (seawater algae). In addition, in order to compare and classify the different families of surfactants, we have included a compilation of toxicity data of surfactants collected from literature. The results indicated that V. fischeri was more sensitive to the toxic effects of the surfactants than was D. magna or the microalgae, which was the least sensitive. This result shows that the most suitable toxicity assay for surfactants may be the one using V. fischeri. The toxicity data revealed considerable variation in toxicity responses with the structure of the surfactants regardless of the species tested. The toxicity data have been related to the structure of the surfactants, giving a mathematical relationship that helps to predict the toxic potential of a surfactant from its structure. Model-predicted toxicity agreed well with toxicity values reported in the literature for several surfactants previously studied. Predictive models of toxicity is a handy tool for providing a risk assessment that can be useful to establish the toxicity range for each surfactant and the different test organisms in order to select efficient surfactants with a lower impact on the aquatic environment.

  17. Piscirickettsia-like organisms as a cause of acute necrotic lesions in Colombian tilapia larvae.

    PubMed

    Iregui, Carlos A; Vasquez, Gersson M; Rey, Alba L; Verjan, Noel

    2011-01-01

    Rickettsial organisms are well-known fish pathogens in both natural and culture environments. This study reports an outbreak of disease in red tilapia larvae caused by piscirickettsia-like organisms (PLOs), which lasted from June until October 2009. Severe mortality was recorded almost exclusively in larvae and postlarvae aged 1-22 days old. Although clinical or gross findings were not evident in diseased fish, histopathology revealed severe necrosis of the epidermis and gill epithelium, with concomitant changes in the underlying skeletal muscle as being the most relevant microscopic lesions. Although PLOs were visible with the routine hematoxylin eosin technique, they were better observed with Giemsa and toluidine blue stains. Transmission electron microscopy revealed that the bacterium was located within the cytoplasm and phagolysosoma-like structures of epithelial cells from the gills and the skin. The bacteria measured 0.9 ± 0.2 µm × 2.1 ± 0.6 µm and had a double cell membrane (the outer one having undulating projections), with variable electron-dense and electron-lucent areas. Ultrastructurally, abundant myelin figures surrounded the microorganisms within host cell cytoplasm. Results indicated that Piscirickettsia-like organisms can cause massive epithelial cell damage associated with concomitant alteration of the electrolyte balance.

  18. Position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients.

    PubMed

    Combes, Alain; Brodie, Daniel; Bartlett, Robert; Brochard, Laurent; Brower, Roy; Conrad, Steve; De Backer, Daniel; Fan, Eddy; Ferguson, Niall; Fortenberry, James; Fraser, John; Gattinoni, Luciano; Lynch, William; MacLaren, Graeme; Mercat, Alain; Mueller, Thomas; Ogino, Mark; Peek, Giles; Pellegrino, Vince; Pesenti, Antonio; Ranieri, Marco; Slutsky, Arthur; Vuylsteke, Alain

    2014-09-01

    The use of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory failure (ARF) in adults is growing rapidly given recent advances in technology, even though there is controversy regarding the evidence justifying its use. Because ECMO is a complex, high-risk, and costly modality, at present it should be conducted in centers with sufficient experience, volume, and expertise to ensure it is used safely. This position paper represents the consensus opinion of an international group of physicians and associated health-care workers who have expertise in therapeutic modalities used in the treatment of patients with severe ARF, with a focus on ECMO. The aim of this paper is to provide physicians, ECMO center directors and coordinators, hospital directors, health-care organizations, and regional, national, and international policy makers a description of the optimal approach to organizing ECMO programs for ARF in adult patients. Importantly, this will help ensure that ECMO is delivered safely and proficiently, such that future observational and randomized clinical trials assessing this technique may be performed by experienced centers under homogeneous and optimal conditions. Given the need for further evidence, we encourage restraint in the widespread use of ECMO until we have a better appreciation for both the potential clinical applications and the optimal techniques for performing ECMO.

  19. Study on acute recent stage pancreatitis

    PubMed Central

    Feng, Ye-Chen; Wang, Min; Zhu, Feng; Qin, Ren-Yi

    2014-01-01

    Acute pancreatitis (AP) is an inflammatory disease of the pancreas which involves the pancreas and surrounding tissue, and systemic inflammation with a characteristic systemic increase of vascular permeability and increased risk of multiple organ dysfunction. Currently, the pathogenesis of AP is fuzzy, and the diagnosis and treatment need to be standardized. Nevertheless, increased knowledge of AP may achieve more thorough understanding of the pathogenesis. The use of further advanced diagnostic tools and superior treatment, potentially will help clinicians to manage AP at an appropriate stage. However, in view of the multi factorial disease and the complex clinical manifestations, the management of patients with AP is also remaining areas for improvement. PMID:25473166

  20. Prognostic markers in acute pancreatitis.

    PubMed

    Gomatos, Ilias P; Xiaodong, Xu; Ghaneh, Paula; Halloran, Christopher; Raraty, Michael; Lane, Brian; Sutton, Robert; Neoptolemos, John P

    2014-04-01

    Acute pancreatitis has a mortality rate of 5-10%. Early deaths are mainly due to multiorgan failure and late deaths are due to septic complications from pancreatic necrosis. The recently described 2012 Revised Atlanta Classification and the Determinant Classification both provide a more accurate description of edematous and necrotizing pancreatitis and local complications. The 2012 Revised Atlanta Classification uses the modified Marshall scoring system for assessing organ dysfunction. The Determinant Classification uses the sepsis-related organ failure assessment scoring system for organ dysfunction and, unlike the 2012 Revised Atlanta Classification, includes infected necrosis as a criterion of severity. These scoring systems are used to assess systemic complications requiring intensive therapy unit support and intra-abdominal complications requiring minimally invasive interventions. Numerous prognostic systems and markers have been evaluated but only the Glasgow system and serum CRP levels provide pragmatic prognostic accuracy early on. Novel concepts using genetic, transcriptomic and proteomic profiling and also functional imaging for the identification of specific disease patterns are now required.

  1. Comparison of the acute toxicities of novel algicides, thiazolidinedione derivatives TD49 and TD53, to various marine organisms.

    PubMed

    Kim, Seong J; Yim, Eun C; Park, In T; Kim, Si W; Cho, Hoon

    2011-12-01

    Acute toxicity assessments of new algicides, thiazolidinedione derivatives TD49 and TD53, to the marine ecological system were conducted. The toxicity assessments were performed using two of the new International Organization for Standardization (ISO) standard methods employing Ulva pertusa Kjellman and three species representative of the marine ecological system, with the results compared by calculating the 50% effective concentration (EC50), 50% lethal concentration (LC50), no-observed-effect concentration (NOEC), and predicted-no-effect concentration (PNEC). In the acute toxicity assessment using the Kjellman, the EC50, NOEC, and PNEC of TD53 were 1.65 µM, 0.08 µM, and 1.65 nM, and those of TD49 were 0.18 µM, 0.63 µM, and 0.18 nM. In the assessments using Skeletonema costatum, Daphnia magna, and Paralichthys olivaceus fry, the EC50 or LC50 of TD53 were 1.53, 0.61, and 2.14 µM, respectively, indicating that D. magna was the most sensitive. The calculated NOEC and PNEC to D. magna were 0.25 µM and 6.10 nM, respectively. The LC50s (or EC50) of TD49 for the three species were 0.34, 0.68, and 0.58 µM. The NOEC and PNEC to S. costatum, the most sensitive species, were 0.2 µM and 3.4 nM, respectively. The slight difference in the chemical structures of the algicides caused significantly different sensitivities and specificities in the toxicities to the employed species. The results of the toxicity assessments showed that application concentrations for algiciding of red tide blooms were higher than the corresponding PNEC values. Therefore, we suggest that a formulization study of the algicides with high specificity should be conducted to reduce the surrounding ecological toxicity.

  2. Predicting the acute neurotoxicity of diverse organic solvents using probabilistic neural networks based QSTR modeling approaches.

    PubMed

    Basant, Nikita; Gupta, Shikha; Singh, Kunwar P

    2016-03-01

    Organic solvents are widely used chemicals and the neurotoxic properties of some are well established. In this study, we established nonlinear qualitative and quantitative structure-toxicity relationship (STR) models for predicting neurotoxic classes and neurotoxicity of structurally diverse solvents in rodent test species following OECD guideline principles for model development. Probabilistic neural network (PNN) based qualitative and generalized regression neural network (GRNN) based quantitative STR models were constructed using neurotoxicity data from rat and mouse studies. Further, interspecies correlation based quantitative activity-activity relationship (QAAR) and global QSTR models were also developed using the combined data set of both rodent species for predicting the neurotoxicity of solvents. The constructed models were validated through deriving several statistical coefficients for the test data and the prediction and generalization abilities of these models were evaluated. The qualitative STR models (rat and mouse) yielded classification accuracies of 92.86% in the test data sets, whereas, the quantitative STRs yielded correlation (R(2)) of >0.93 between the measured and model predicted toxicity values in both the test data (rat and mouse). The prediction accuracies of the QAAR (R(2) 0.859) and global STR (R(2) 0.945) models were comparable to those of the independent local STR models. The results suggest the ability of the developed QSTR models to reliably predict binary neurotoxicity classes and the endpoint neurotoxicities of the structurally diverse organic solvents.

  3. Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure

    PubMed Central

    Baker, Luisa A.; Lee, Karla C. L.; Palacios Jimenez, Carolina; Alibhai, Hatim; Chang, Yu-Mei; Leckie, Pamela J.; Mookerjee, Rajeshwar P.; Davies, Nathan A.; Andreola, Fausto; Jalan, Rajiv

    2015-01-01

    Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002). Conclusions MicroRNAs were released passively into the circulation in response to acetaminophen-induced cellular damage. A significant increase in global microRNA was detectable prior to significant increases in miR122, miR192 and miR124-1, which were associated with clinical evidence of liver, kidney and brain injury respectively. PMID:26018205

  4. Acute Pancreatitis: The Role of Imaging and Interventional Radiology

    SciTech Connect

    Maher, Michael M.; Lucey, Brian C.; Gervais, Debra A.; Mueller, Peter R.

    2004-09-15

    Acute pancreatitis can manifest as a benign condition with minimal abdominal pain and hyperamylasemia or can have a fulminant course, which can be life-threatening usually due to the development of infected pancreatic necrosis, and multisystem organ failure. Fortunately, 70-80% of patients with acute pancreatitis have a benign self-limiting course. The initial 24-48 hours after the initial diagnosis is usually the period that determines the subsequent course, and for many of the 20-30% of patients who subsequently have a fulminant course, this becomes apparent within this time frame. With reference to long-term outcome following acute pancreatitis, most cases recover without long-term sequelae with only a minority of cases progressing to chronic pancreatitis. In the initial management of acute pancreatitis, assessment of metabolic disturbances and systemic organ dysfunction is critical. However, the advent and continued refinement of cross-sectional imaging modalities over the past two decades has led to a prominent role for diagnostic imaging in assessing acute pancreatitis. Furthermore, these cross-sectional imaging modalities have enabled the development of diagnostic and therapeutic interventional techniques in the hands of radiologists. In this article we review the diagnostic features of acute pancreatitis, the clinical staging systems, complications and the role of imaging. The role of interventional radiology techniques in the management of acute pancreatitis will be discussed as well as potential complications associated with these treatments.

  5. Mitochondrial dysfunction and organophosphorus compounds

    SciTech Connect

    Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

    2013-07-01

    Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP.

  6. Markers of erectile dysfunction

    PubMed Central

    Davies, Kelvin P.; Melman, Arnold

    2008-01-01

    With the development and marketing of oral pharmacotherapy that is both noninvasive and successful in treating erectile dysfunction (ED), the quest to identify markers of organic ED lost ground. Indeed, the multi-factorial nature of ED may have led many researchers to conclude that searching for a universal marker of ED was futile. However, the realization that ED is strongly correlated with the overall health of men, and may act as a predictor for the development of cardiovascular disease (CVD) and diabetes, has stimulated interest in identifying genes that can distinguish organic ED. In addition, the potential ability to suggest to the patient that ED is reversible (i.e., psychogenic) with a simple test would be of significance to both the physician and patient, as well as for reimbursement issues for therapy by insurance companies. Such a marker may also act as a non-subjective measure of the degree of ED and the efficacy of treatment. This review discusses the importance of identifying such markers and recent work identifying potential markers in human patients. PMID:19468461

  7. Acute effects and exposure to organic compounds in road maintenance workers exposed to asphalt.

    PubMed

    Norseth, T; Waage, J; Dale, I

    1991-01-01

    Subjective symptoms and exposure to organic compounds were recorded in road repair and construction workers. Abnormal fatigue, reduced appetite, laryngeal/pharyngeal irritation, and eye irritation were recorded more often in such workers handling asphalt than in a corresponding reference group without asphalt exposure. Mean daily exposure to volatile compounds was only occasionally above 1 ppm. Mean exposure to asphalt fume was 0.358 mg/m3. There was no correlation between symptoms and total amount of volatile compounds, but a significant positive correlation was demonstrated between symptoms and some substances. The highest correlation was found for 1, 2, 4 trimethyl benzene. Symptoms increased with increasing asphalt temperature and with increasing concentrations of asphalt fumes. Amine addition did not increase the sum of symptoms, but soft asphalt seems to result in fewer symptoms than the harder types. Symptoms were not related to external factors like weather, traffic density, or specific working operations. As preventive measures, asphalt temperature should be kept below 150 degrees C, fume concentrations below 0.40 mg/m3, and if possible, the use of harder asphalt types which also require high temperatures should be avoided.

  8. Asthma: vocal cord dysfunction (VCD) and other dysfunctional breathing disorders.

    PubMed

    Balkissoon, Ron; Kenn, Klaus

    2012-12-01

    Vocal cord dysfunction (VCD) and dysfunctional breathing (DB) disorders may mimic or coexist with asthma, leading to overtreatment with corticosteroids with consequent morbidity. Iatrogenic complications can be averted by early and correct diagnosis. VCD, also termed paradoxical vocal fold motion disorder (PVFMD), is characterized by intermittent paradoxical adduction of the vocal cords, mainly during inspiration, leading to airflow obstruction and dyspnea. Patients with VCD may have repetitive emergency room visits due to acute dyspnea (mimicking exacerbations of asthma). In the seminal descriptions of VCD, young women (often with psychiatric issues) predominated; however, other groups at increased risk for developing VCD include elite athletes, military recruits, and individuals exposed to irritants (inhaled or aspirated). Chronic postnasal drip, laryngopharyngeal reflux (LPR), and gastroesophageal reflux (GER) may lead to laryngeal hyperresponsiveness. The diagnosis of VCD may be difficult because physical exam and spirometry may be normal between episodes. During symptomatic episodes, spirometry typically reveals variable extrathoracic airway obstruction (truncated inspiratory flow volume loop). The gold standard for identifying VCD is flexible fiberoptic rhinolaryngoscopy. Management of VCD includes identification and treatment of underlying disorders (eg, chronic postnasal drip, LPR, GER, anxiety, depression) and a multidisciplinary approach (including highly trained speech therapists). Speech therapy and biofeedback play a critical role in teaching techniques to override various dysfunctional breathing habits. When postnasal drip, LPR, or GER coexist, these disorders should be aggressively treated. With successful therapy, corticosteroids can often be discontinued. During severe, acute episodes of VCD, therapeutic strategies include heliox (80% helium/20% oxygen), topical lidocaine, anxiolytics, and superior laryngeal blocks with Clostridium botulinum toxin

  9. Extrapancreatic organ impairment during acute pancreatitis induced by bile-pancreatic duct obstruction. Effect of N-acetylcysteine

    PubMed Central

    Manso, Manuel A; Ramudo, Laura; De Dios, Isabel

    2007-01-01

    Summary Multiple organ failure is frequently associated with acute pancreatitis (AP). Our aim was to study pulmonary, hepatic and renal complications developed in the course of AP experimentally induced in rats by bile-pancreatic duct obstruction (BPDO), differentiating the complications caused by AP itself, from those directly caused by bile duct obstruction (BDO), after ligating the choledocus. N-acetylcysteine (NAC) was administered as a therapeutic approach. Myeloperoxidase activity revealed neutrophil infiltration in lungs from 12 h after BDO, even if AP was not triggered. Lactate dehydrogenase (LDH) activity indicated hepatocyte death from 48 h after BDO, and from 24 h following BPDO-induced AP onwards, an effect delayed until 48 h by NAC treatment. Rats with single cholestasis (BDO) and rats with BPDO-induced AP showed a significant increase in plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin concentration from 12 h onwards, whose values were reduced by NAC treatment at early BPDO. No renal failure was found during 120 h of bile-pancreatic obstruction. Our results showed lung and liver impairment as a result of BDO, even if AP does not develop. Pancreatic damage and extrapancreatic complications during AP induced by BPDO were palliated by NAC treatment. PMID:17877536

  10. Effectiveness of contact precautions against multidrug-resistant organism transmission in acute care: a systematic review of the literature.

    PubMed

    Cohen, C C; Cohen, B; Shang, J

    2015-08-01

    Contact precautions are widely recommended to prevent multidrug-resistant organism (MDRO) transmission. However, conflicting data exist regarding their effectiveness. Prior systematic reviews examined contact precautions as part of a larger bundled approach, limiting ability to understand their effectiveness. The aim of this review was to characterize the effectiveness of contact precautions alone against transmission of any MDRO among adult acute care patients. Directed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, comprehensive searches of four electronic scientific literature databases were conducted for studies published in English from January 2004 to June 2014. Studies were included if interventional, original research, evaluating contact isolation precautions against MDRO transmission among inpatients. Searches returned 284 studies, six of which were included in the review. These studies measured four different MDROs with one study showing a reduction in transmission. Whereas studies were of high quality regarding outcome operationalization and statistical analyses, overall quality was moderate to low due to poor intervention description, population characterization and potential biases. Where compliance was measured (N = 4), it presented a threat to validity because it included select parts of the intervention, ranged from 21% to 87%, and was significantly different across study phases (N = 2). The poor quality of evidence on this topic continues to limit interpretation of these data. Hence, this conflicting body of literature does not constitute evidence for or against contact precautions. We recommend that researchers consider power calculation, compliance monitoring, non-equivalent concurrent controls when designing future studies on this topic.

  11. A simultaneous multiple species acute toxicity test comparing relative sensitivities of six aquatic organisms to HgCl{sub 2}

    SciTech Connect

    McCrary, J.E.; Heagler, M.G.

    1995-12-31

    In the last few years there has been concern in the scientific community about observed declines in some amphibian species. These population declines could be reflecting a global phenomenon due to a general class sensitivity or may be part of a natural cycle. The suggestion of an overall greater sensitivity of amphibians is not supported. Studies show that amphibians, as a class, are neither more or less susceptible than fish to environmental conditions. Mercury has been found to be one of the most toxic of the heavy metals introduced into amphibian breeding waters. Six aquatic species were simultaneously exposed in a comparative acute toxicity test with mercury chloride: three amphibians, Rana catesbeiana (bullfrog), R. clamitans (green frog), and R. sphenocephala (southern leopard frog, formally classified as R. utricularia); two fish, Gambusia affinis (mosquitofish) and Notemigonus crysoleucas (golden shiner); one aquatic aligochaete, Lumbriculus variegatus (aquatic earthworm). The five test concentrations used were 1.4, 3.9, 12.0, 110.0, and 487.0 {micro}g Hg/L respectively. Ten organisms per species were randomly placed into the six test tanks (control and five concentrations), each species in a separate chamber. The resultant LC50-96hr values produced the following rank order: R. sphenocephala, 6.59 {micro}g Hg/L; R. clamitans, 14.7 {micro}g Hg/L; N. crysoleucas, 16.75 {micro}g Hg/L; L. variegatus, 43.72,ug Hg/L; G. affinis, 52.62 {micro}g Hg/L; R. catesbeiana, 63.36 {micro}g Hg/L. No general organism class sensitivity trend, for amphibians, was developed from this data, contrary to the implicit suggestions of some researchers.

  12. Establishment and Characterization of an Air-Liquid Canine Corneal Organ Culture Model To Study Acute Herpes Keratitis

    PubMed Central

    Harman, Rebecca M.; Bussche, Leen; Ledbetter, Eric C.

    2014-01-01

    ABSTRACT Despite the clinical importance of herpes simplex virus (HSV)-induced ocular disease, the underlying pathophysiology of the disease remains poorly understood, in part due to the lack of adequate virus–natural-host models in which to study the cellular and viral factors involved in acute corneal infection. We developed an air-liquid canine corneal organ culture model and evaluated its susceptibility to canine herpesvirus type 1 (CHV-1) in order to study ocular herpes in a physiologically relevant natural host model. Canine corneas were maintained in culture at an air-liquid interface for up to 25 days, and no degenerative changes were observed in the corneal epithelium during cultivation using histology for morphometric analyses, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assays, and transmission electron microscopy (TEM). Next, canine corneas were inoculated with CHV-1 for 48 h, and at that time point postinfection, viral plaques could be visualized in the corneal epithelium and viral DNA copies were detected in both the infected corneas and culture supernatants. In addition, we found that canine corneas produced proinflammatory cytokines in response to CHV-1 infection similarly to what has been described for HSV-1. This emphasizes the value of our model as a virus–natural-host model to study ocular herpesvirus infections. IMPORTANCE This study is the first to describe the establishment of an air-liquid canine corneal organ culture model as a useful model to study ocular herpesvirus infections. The advantages of this physiologically relevant model include the fact that (i) it provides a system in which ocular herpes can be studied in a virus–natural-host setting and (ii) it reduces the number of experimental animals needed. In addition, this long-term explant culture model may also facilitate research in other fields where noninfectious and infectious ocular diseases of dogs and humans are being studied. PMID

  13. Practical approach on frail older patients attended for acute heart failure.

    PubMed

    Martín-Sánchez, Francisco J; Christ, Michael; Miró, Òscar; Peacock, W Frank; McMurray, John J; Bueno, Héctor; Maisel, Alan S; Cullen, Louise; Cowie, Martin R; Di Somma, Salvatore; Platz, Elke; Masip, Josep; Zeymer, Uwe; Vrints, Christiaan; Price, Susanna; Mueller, Christian

    2016-11-01

    Acute heart failure (AHF) is a multi-organ dysfunction syndrome. In addition to known cardiac dysfunction, non-cardiac comorbidity, frailty and disability are independent risk factors of mortality, morbidity, cognitive and functional decline, and risk of institutionalization. Frailty, a treatable and potential reversible syndrome very common in older patients with AHF, increases the risk of disability and other adverse health outcomes. This position paper highlights the need to identify frailty in order to improve prognosis, the risk-benefits of invasive diagnostic and therapeutic procedures, and the definition of older-person-centered and integrated care plans.

  14. Effect of Da-Cheng-Qi Decoction on the Repair of the Injured Enteric Nerve-Interstitial Cells of Cajal-Smooth Muscle Cells Network in Multiple Organ Dysfunction Syndrome

    PubMed Central

    Liu, Mu-Cang; Xie, Ming-Zheng; Ma, Bin; Qi, Qing-Hui

    2014-01-01

    Wistar rats were randomly divided into control group, multiple organ dysfunction syndrome (MODS) group, and Da-Cheng-Qi decoction (DCQD) group. The network of enteric nerves-interstitial cells of Cajal- (ICC-) smooth muscle cells (SMC) in small intestine was observed using confocal laser scanning microscopy and transmission electron microscopy. The results showed that the numbers of cholinergic/nitriergic nerves, and the deep muscular plexus of ICC (ICC-DMP) and connexin43 (Cx43) in small intestine with MODS were significantly decreased. The network integrity of enteric nerves-ICC-SMC was disrupted. The ultrastructures of ICC-DMP, enteric nerves, and SMC were severely damaged. After treatment with DCQD, the damages were repaired and the network integrity of enteric nerves ICC-SMC was significantly recovered. In conclusion, the pathogenesis of gastrointestinal motility dysfunction in MODS in part may be due to the damages to enteric nerves-ICC-SMC network and gap junctions. The therapeutic mechanism of DCQD in part may be that it could repair the damages and maintain the integrity of enteric nerves ICC-SMC network. PMID:25477993

  15. Vascular dysfunctions following spinal cord injury

    PubMed Central

    Popa, F; Grigorean, VT; Onose, G; Sandu, AM; Popescu, M; Burnei, G; Strambu, V; Sinescu, C

    2010-01-01

    The aim of this article is to analyze the vascular dysfunctions occurring after spinal cord injury (SCI). Vascular dysfunctions are common complications of SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. Neuroanatomy and physiology of autonomic nervous system, sympathetic and parasympathetic, is reviewed. SCI implies disruption of descendent pathways from central centers to spinal sympathetic neurons, originating in intermediolateral nuclei of T1–L2 cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant vascular dysfunction. Spinal shock occurs during the acute phase following SCI and it is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe arterial hypotension and bradycardia. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Arterial hypotension with orthostatic hypotension occurs in both acute and chronic phases. The etiology is multifactorial. We described a few factors influencing the orthostatic hypotension occurrence in SCI: sympathetic nervous system dysfunction, low plasma catecholamine levels, rennin–angiotensin–aldosterone activity, peripheral alpha–adrenoceptor hyperresponsiveness, impaired function of baroreceptors, hyponatremia and low plasmatic volume, cardiovascular deconditioning, morphologic changes in sympathetic neurons, plasticity within spinal circuits, and motor deficit leading to loss of skeletal muscle pumping activity. Additional associated cardiovascular concerns in SCI, such as

  16. Acute and chronic toxicity toward the bacteria Vibrio fischeri of organic narcotics and epoxides: structural alerts for epoxide excess toxicity.

    PubMed

    Blaschke, Ulrike; Paschke, Albrecht; Rensch, Ines; Schüürmann, Gerrit

    2010-12-20

    The acute and chronic bacterial toxicity of 34 organic compounds comprising 19 baseline narcotics and 15 epoxides has been determined with regard to 30-min bioluminescence and 24-h growth inhibition in terms of EC50 (effective concentration 50%) values employing Vibrio fischeri. For the narcotics, linear regression of log EC50 on log Kow (octanol/water partition coefficient) yields r2 (squared correlation coefficient) and rms (root-mean-square error) values of 0.95 and 0.44 (30-min), and 0.94 and 0.34 (24-h), respectively. Employing the resultant baseline narcosis models, toxicity enhancement (Te) values were derived as a ratio of narcosis-predicted over experimental EC50 for the epoxides. For seven aliphatic epoxides, log Te was below 1 in both assays, indicating narcosis-range toxicity with regard to 30-min bioluminescence and 24-h growth inhibition. Concerning eight nonaliphatic epoxides, log Te values up to 2.4 were observed, reflecting excess toxicity through an enhanced electrophilic reactivity of the compounds. Here, however, the intercorrelation between both assays was very low (r2 = 0.09). The results are discussed in terms of electronic substituent effects activating an SN2-type epoxide reaction with nucleophilic protein sites and side-chain activation offering alternative electrophile-nucleophile reaction routes at side-chain sites, leading to respective structural alerts as indicators of excess toxicity. Surprisingly, 30-min bioluminescence appears to be slightly more sensitive to chemical stress than 24-h growth, which holds both for baseline narcotics and for most of the epoxides. This is also reflected by effective narcosis doses 50%, ED50, of 7.1 mmol/kg (30-min) and 7.7 mmol/kg (24-h) estimated from narcosis theory. Keeping in mind the different end points (bioluminescence vs growth) involved, this finding demonstrates that chronic toxicity is not always more sensitive than acute toxicity, calling for analyses with regard to further respective

  17. DNA repair in ischemic acute kidney injury.

    PubMed

    Pressly, Jeffrey D; Park, Frank

    2017-04-01

    Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury leading to an induction of oxidative stress, cellular dysfunction, and loss of renal function. DNA damage, including oxidative base modifications and physical DNA strand breaks, is a consequence of renal IRI. Like many other organs in the body, a redundant and highly conserved set of endogenous repair pathways have evolved to selectively recognize the various types of cellular DNA damage and combat its negative effects on cell viability. Severe damage to the DNA, however, can trigger cell death and elimination of the injured tubular epithelial cells. In this minireview, we summarize the state of the current field of DNA damage and repair in the kidney and provide some expected and, in some cases, unexpected effects of IRI on DNA damage and repair in the kidney. These findings may be applicable to other forms of acute kidney injury and could provide new opportunities for renal research.

  18. THE PROLONGED GASTROINTESTINAL SYNDROME IN RHESUS MACAQUES: THE RELATIONSHIP BETWEEN GASTROINTESTINAL, HEMATOPOIETIC, AND DELAYED MULTI-ORGAN SEQUELAE FOLLOWING ACUTE, POTENTIALLY LETHAL, PARTIAL-BODY IRRADIATION

    PubMed Central

    MacVittie, Thomas J.; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M.

    2014-01-01

    The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min−1 to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for

  19. Impacts of environmental toxicants on male reproductive dysfunction

    PubMed Central

    Wong, Elissa W.P.; Cheng, C. Yan

    2011-01-01

    Male infertility caused by exposure to environmental toxicants, such as cadmium, mercury, bisphenol A (BPA) and dioxin, is a global problem, particularly in industrialized countries. Studies in the testis and other organs have illustrated the importance of environmental toxicant-induced oxidative stress in mediating disruption to cell junctions. This, in turn, is regulated by the activation of PI3K/c-Src/FAK and MAPK signaling pathways, with the involvement of polarity proteins, leading to reproductive dysfunction, such as reduced sperm count and semen quality in men. In this review, we discuss how these findings can improve understanding of the modes of action of environmental toxicants in –testicular dysfunction. Thus, specific inhibitors and/or antagonists against signaling molecules in these pathways can possibly reverse and/or block the disruptive effects of toxicant-induced damage. Additional studies comparing high level acute exposure versus low level chronic exposure to environmental toxicants are also needed to elucidate fully the underlying molecular mechanism(s) by which these toxicants disrupt male reproductive function. PMID:21324536

  20. Development of a salinity/toxicity relationship to predict acute toxicity of saline waters to freshwater organisms. Interim final report, June 1990-March 1992

    SciTech Connect

    Mount, D.R.; Gulley, D.D.

    1992-04-01

    Discharge of produced water to surface waters is generally regulated as part of the NPDES permit problem and, therefore, may be subject to discharge limits for aquatic toxicity. Most produced waters contain elevated (relative to fresh water) concentrations of major ions (e.g., sodium, chloride) that can be toxic to fresh water organisms regardless of other organic and inorganic constituents. The objective of the research was to develop a Salinity/Toxicity Relationship (STR) that predicts the acute toxicity of saline waters to freshwater organisms based on the concentrations of major ions in solution. Laboratory toxicity tests were conducted to measure the acute toxicity of major ions to three freshwater species (Ceriodaphnia dubia, Daphnia magna, and fathead minnows). These laboratory toxicity data were then incorporated into multi-variate logistic regression equations that predict the acute toxicity of any combination of major ions. Logistic regression equations represented the toxicity data quite well, generally explaining in excess of 80 percent of the overall variance in survival. Application of the Ceriodaphnia STR to field data collected from surface waters receiving produced water discharges showed very strong correlation of STR predictions with the results of toxicity tests conducted on field-collected samples.

  1. Marital sexual dysfunction:introductory concepts.

    PubMed

    Levine, S B

    1976-04-01

    The concepts presented in this overview of marital sexual dysfunction are derived from increasing clinical experience with couples who seek help for their sexual problems. These couples, in marked contrast to couples with good sexual functioning, usually report a steady state of emotional dissatisfaction and minimal physical pleasure from sex. The affectual and behavioral consequences of persistent dysfunction are reviewed. Sexual therapy is discussed in terms of its two elements, sensate focus and psychotherapy. The various tastks which the sexual therapist may have to accomplish with individual couples are described. Consideration is given to the specific hypothese usually offered as explanation for sexual dysfunction-i.e., organic factors, varying degrees of relationship failure, poor communication, sexual ignorance, performance anxiety, and intrapsychic residua of past experience. A protocol for the screening physician to use in the formulation of a reasonable clinical plan for dysfunctional couples is included.

  2. Current concepts in organic acidurias: understanding intra- and extracerebral disease manifestation.

    PubMed

    Kölker, Stefan; Burgard, Peter; Sauer, Sven W; Okun, Jürgen G

    2013-07-01

    This review focuses on the pathophysiology of organic acidurias (OADs), in particular, OADs caused by deficient amino acid metabolism. OADs are termed classical if patients present with acute metabolic decompensation and multiorgan dysfunction or cerebral if patients predominantly present with neurological symptoms but without metabolic crises. In both groups, however, the brain is the major target. The high energy demand of the brain, the gate-keeping function of the blood-brain barrier, a high lipid content, vulnerable neuronal subpopulations, and glutamatergic neurotransmission all make the brain particularly vulnerable against mitochondrial dysfunction, oxidative stress, and excitotoxicity. In fact, toxic metabolites in OADs are thought to cause secondary impairment of energy metabolism; some of these toxic metabolites are trapped in the brain. In contrast to cerebral OADs, patients with classical OADs have an increased risk of multiorgan dysfunction. The lack of the anaplerotic propionate pathway, synergistic inhibition of energy metabolism by toxic metabolites, and multiple oxidative phosphorylation (OXPHOS) deficiency may best explain the involvement of organs with a high energy demand. Intriguingly, late-onset organ dysfunction may manifest even under metabolically stable conditions. This might be explained by chronic mitochondrial DNA depletion, increased production of reactive oxygen species, and altered gene expression due to histone modification. In conclusion, pathomechanisms underlying the acute disease manifestation in OADs, with a particular focus on the brain, are partially understood. More work is required to predict the risk and to elucidate the mechanism of late-onset organ dysfunction, extracerebral disease manifestation, and tumorigenesis.

  3. Influence of dissolved organic carbon on toxicity of copper to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) in acute and chronic water exposures

    USGS Publications Warehouse

    Wang, Ning; Mebane, Christopher A.; Kunz, James L.; Ingersoll, Christopher G.; Brumbaugh, William G.; Santore, Robert C.; Gorsuch, Joseph W.; Arnold, W. Ray

    2011-01-01

    Acute and chronic toxicity of copper (Cu) to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) were determined in water exposures at four concentrations of dissolved organic carbon (DOC; nominally 0.5, 2.5, 5, and 10 mg/L as carbon [C]). Test waters with DOC concentrations of 2.5 to 10 mg C/L were prepared by mixing a concentrate of natural organic matter (Suwannee River, GA, USA) in diluted well water (hardness 100 mg/L as CaCO3, pH 8.3, DOC 0.5 mg C/L). Acute median effect concentrations (EC50s) for dissolved Cu increased approximately fivefold (15–72 μg Cu/L) for mussel survival in 4-d exposures and increased about 11-fold (25–267 μg Cu/L) for cladoceran survival in 2-d exposures across DOC concentrations from 0.5 to 10 mg C/L. Similarly, chronic 20% effect concentrations (EC20s) for the mussel in 28-d exposures increased about fivefold (13–61 μg Cu/L for survival; 8.8–38 μg Cu/L for biomass), and the EC20s for the cladoceran in 7-d exposures increased approximately 17-fold (13–215 μg Cu/L) for survival or approximately fourfold (12–42 μg Cu/L) for reproduction across DOC concentrations from 0.5 to 10 mg C/L. The acute and chronic values for the mussel were less than or approximately equal to the values for the cladoceran. Predictions from the biotic ligand model (BLM) used to derive the U.S. Environmental Protection Agency's ambient water quality criteria (AWQC) for Cu explained more than 90% of the variation in the acute and chronic endpoints for the two species, with the exception of the EC20 for cladoceran reproduction (only 46% of variation explained). The BLM-normalized acute EC50s and chronic EC20s for the mussel and BLM-normalized chronic EC20s for the cladoceran in waters with DOC concentrations of 2.5 to 10 mg C/L were equal to or less than the final acute value and final chronic value in the BLM-based AWQC for Cu, respectively, indicating that the Cu AWQC might not adequately protect the mussel from acute and

  4. Influence of dissolved organic carbon on toxicity of copper to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) in acute and chronic water exposures.

    PubMed

    Wang, Ning; Mebane, Christopher A; Kunz, James L; Ingersoll, Christopher G; Brumbaugh, William G; Santore, Robert C; Gorsuch, Joseph W; Arnold, W Ray

    2011-09-01

    Acute and chronic toxicity of copper (Cu) to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) were determined in water exposures at four concentrations of dissolved organic carbon (DOC; nominally 0.5, 2.5, 5, and 10 mg/L as carbon [C]). Test waters with DOC concentrations of 2.5 to 10 mg C/L were prepared by mixing a concentrate of natural organic matter (Suwannee River, GA, USA) in diluted well water (hardness 100 mg/L as CaCO(3) , pH 8.3, DOC 0.5 mg C/L). Acute median effect concentrations (EC50s) for dissolved Cu increased approximately fivefold (15-72 µg Cu/L) for mussel survival in 4-d exposures and increased about 11-fold (25-267 µg Cu/L) for cladoceran survival in 2-d exposures across DOC concentrations from 0.5 to 10 mg C/L. Similarly, chronic 20% effect concentrations (EC20s) for the mussel in 28-d exposures increased about fivefold (13-61 µg Cu/L for survival; 8.8-38 µg Cu/L for biomass), and the EC20s for the cladoceran in 7-d exposures increased approximately 17-fold (13-215 µg Cu/L) for survival or approximately fourfold (12-42 µg Cu/L) for reproduction across DOC concentrations from 0.5 to 10 mg C/L. The acute and chronic values for the mussel were less than or approximately equal to the values for the cladoceran. Predictions from the biotic ligand model (BLM) used to derive the U.S. Environmental Protection Agency's ambient water quality criteria (AWQC) for Cu explained more than 90% of the variation in the acute and chronic endpoints for the two species, with the exception of the EC20 for cladoceran reproduction (only 46% of variation explained). The BLM-normalized acute EC50s and chronic EC20s for the mussel and BLM-normalized chronic EC20s for the cladoceran in waters with DOC concentrations of 2.5 to 10 mg C/L were equal to or less than the final acute value and final chronic value in the BLM-based AWQC for Cu, respectively, indicating that the Cu AWQC might not adequately protect the mussel from acute and

  5. Influence of dissolved organic carbon on toxicity of copper to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) in acute and chronic water exposures

    USGS Publications Warehouse

    Wang, N.; Mebane, C.A.; Kunz, J.L.; Ingersoll, C.G.; Brumbaugh, W.G.; Santore, R.C.; Gorsuch, J.W.; Arnold, W.R.

    2011-01-01

    Acute and chronic toxicity of copper (Cu) to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) were determined in water exposures at four concentrations of dissolved organic carbon (DOC; nominally 0.5, 2.5, 5, and 10mg/L as carbon [C]). Test waters with DOC concentrations of 2.5 to 10mgC/L were prepared by mixing a concentrate of natural organic matter (Suwannee River, GA, USA) in diluted well water (hardness 100mg/L as CaCO3, pH 8.3, DOC 0.5mgC/L). Acute median effect concentrations (EC50s) for dissolved Cu increased approximately fivefold (15-72??gCu/L) for mussel survival in 4-d exposures and increased about 11-fold (25-267??gCu/L) for cladoceran survival in 2-d exposures across DOC concentrations from 0.5 to 10mgC/L. Similarly, chronic 20% effect concentrations (EC20s) for the mussel in 28-d exposures increased about fivefold (13-61??gCu/L for survival; 8.8-38??gCu/L for biomass), and the EC20s for the cladoceran in 7-d exposures increased approximately 17-fold (13-215??gCu/L) for survival or approximately fourfold (12-42??gCu/L) for reproduction across DOC concentrations from 0.5 to 10mgC/L. The acute and chronic values for the mussel were less than or approximately equal to the values for the cladoceran. Predictions from the biotic ligand model (BLM) used to derive the U.S. Environmental Protection Agency's ambient water quality criteria (AWQC) for Cu explained more than 90% of the variation in the acute and chronic endpoints for the two species, with the exception of the EC20 for cladoceran reproduction (only 46% of variation explained). The BLM-normalized acute EC50s and chronic EC20s for the mussel and BLM-normalized chronic EC20s for the cladoceran in waters with DOC concentrations of 2.5 to 10mgC/L were equal to or less than the final acute value and final chronic value in the BLM-based AWQC for Cu, respectively, indicating that the Cu AWQC might not adequately protect the mussel from acute and chronic exposure, and the cladoceran

  6. Neuroanatomy and Physiology of Brain Dysfunction in Sepsis.

    PubMed

    Mazeraud, Aurelien; Pascal, Quentin; Verdonk, Franck; Heming, Nicholas; Chrétien, Fabrice; Sharshar, Tarek

    2016-06-01

    Sepsis-associated encephalopathy (SAE), a complication of sepsis, is often complicated by acute and long-term brain dysfunction. SAE is associated with electroencephalogram pattern changes and abnormal neuroimaging findings. The major processes involved are neuroinflammation, circulatory dysfunction, and excitotoxicity. Neuroinflammation and microcirculatory alterations are diffuse, whereas excitotoxicity might occur in more specific structures involved in the response to stress and the control of vital functions. A dysfunction of the brainstem, amygdala, and hippocampus might account for the increased mortality, psychological disorders, and cognitive impairment. This review summarizes clinical and paraclinical features of SAE and describes its mechanisms at cellular and structural levels.

  7. Organic Nitrates and Nitrate Resistance in Diabetes: The Role of Vascular Dysfunction and Oxidative Stress with Emphasis on Antioxidant Properties of Pentaerithrityl Tetranitrate

    PubMed Central

    Oelze, Matthias; Schuhmacher, Swenja; Daiber, Andreas

    2010-01-01

    Organic nitrates represent a class of drugs which are clinically used for treatment of ischemic symptoms of angina as well as for congestive heart failure based on the idea to overcome the impaired NO bioavailability by “NO” replacement therapy. The present paper is focused on parallels between diabetes mellitus and nitrate tolerance, and aims to discuss the mechanisms underlying nitrate resistance in the setting of diabetes. Since oxidative stress was identified as an important factor in the development of tolerance to organic nitrates, but also represents a hallmark of diabetic complications, this may represent a common principle for both disorders where therapeutic intervention should start. This paper examines the evidence supporting the hypothesis that pentaerithrityl tetranitrate may represent a nitrate for treatment of ischemia in diabetic patients. This evidence is based on the considerations of parallels between diabetes mellitus and nitrate tolerance as well as on preliminary data from experimental diabetes studies. PMID:21234399

  8. Organic nitrates and nitrate resistance in diabetes: the role of vascular dysfunction and oxidative stress with emphasis on antioxidant properties of pentaerithrityl tetranitrate.

    PubMed

    Oelze, Matthias; Schuhmacher, Swenja; Daiber, Andreas

    2010-01-01

    Organic nitrates represent a class of drugs which are clinically used for treatment of ischemic symptoms of angina as well as for congestive heart failure based on the idea to overcome the impaired NO bioavailability by "NO" replacement therapy. The present paper is focused on parallels between diabetes mellitus and nitrate tolerance, and aims to discuss the mechanisms underlying nitrate resistance in the setting of diabetes. Since oxidative stress was identified as an important factor in the development of tolerance to organic nitrates, but also represents a hallmark of diabetic complications, this may represent a common principle for both disorders where therapeutic intervention should start. This paper examines the evidence supporting the hypothesis that pentaerithrityl tetranitrate may represent a nitrate for treatment of ischemia in diabetic patients. This evidence is based on the considerations of parallels between diabetes mellitus and nitrate tolerance as well as on preliminary data from experimental diabetes studies.

  9. [Investigations of the distribution of aripiprazole in the internal organs and biological fluids of the laboratory animals in case of acute intoxication].

    PubMed

    Voronkov, A V; Remezova, I P; Lazaryan, D S; Avramenko, N S; Rybasova, A S

    2015-01-01

    Despite the present-day extensive application of aripiprazole, there are many cases of its overdose and of poisoning with this compound. The objective of the present study was to detect and quantify aripiprazole in the internal organs and biological fluids of the laboratory animals in case of acute intoxication. The experiments were carried out on white mice of both sexes weighing 20.5 and 25.7 g. Aripiprazole was isolated from the liver, kidneys, brain, and heart as described by A.A. Vasil'eva and from the plasma and urine by the newly developed original methods. Aripiprazole was identified and quantitatively determined in the extracts from the aforementioned organs and tissues with the use of HPLC. The data obtained on the completeness of extraction from the liver, kidneys , and brain of the laboratory animals indicate that aripiprazole accumulated in the highest concentrations in the brain and kidneys within 24 hours after acute poisoning. Ist content was significantly lower in the liver while no traces of aripiprazole were found in the heart of the mice. The methods for aripiprazole isolation from the urine and blood plasma are described. The maximum amounts of aripiprazole were detected in blood plasma within 24 hours after acute intoxication. It is concluded that the proposed methods for aripiprazole isolation from the biological fluids (blood plasma and urine) can be included in the scheme of the chemical toxicological analysis of this compound.

  10. Axillary nerve dysfunction

    MedlinePlus

    ... Causes Axillary nerve dysfunction is a form of peripheral neuropathy . It occurs when there is damage to the ... Multiple mononeuropathy Muscle function loss Numbness and tingling Peripheral neuropathy Systemic Review Date 2/3/2015 Updated by: ...

  11. Tibial nerve dysfunction

    MedlinePlus

    ... Tibial nerve dysfunction is an unusual form of peripheral neuropathy . It occurs when there is damage to the ... PA: Elsevier Saunders; 2012:chap 76. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman-Cecil ...

  12. Chronic pelvic floor dysfunction.

    PubMed

    Hartmann, Dee; Sarton, Julie

    2014-10-01

    The successful treatment of women with vestibulodynia and its associated chronic pelvic floor dysfunctions requires interventions that address a broad field of possible pain contributors. Pelvic floor muscle hypertonicity was implicated in the mid-1990s as a trigger of major chronic vulvar pain. Painful bladder syndrome, irritable bowel syndrome, fibromyalgia, and temporomandibular jaw disorder are known common comorbidities that can cause a host of associated muscular, visceral, bony, and fascial dysfunctions. It appears that normalizing all of those disorders plays a pivotal role in reducing complaints of chronic vulvar pain and sexual dysfunction. Though the studies have yet to prove a specific protocol, physical therapists trained in pelvic dysfunction are reporting success with restoring tissue normalcy and reducing vulvar and sexual pain. A review of pelvic anatomy and common findings are presented along with suggested physical therapy management.

  13. Sexual Dysfunction in Women

    MedlinePlus

    ... pressure), excessive alcohol use or vaginal infections can cause sexual problems. Depression, relationship problems or abuse (current or past abuse) can also cause sexual dysfunction.You may have less sexual desire ...

  14. Temporomandibular Joint Dysfunction

    MedlinePlus

    The temporomandibular joint (TMJ) connects your jaw to the side of your head. When it works well, it enables you to ... For people with TMJ dysfunction, problems with the joint and muscles around it may cause Pain that ...

  15. Sexual Dysfunction in Women

    PubMed Central

    Brown, Pamela

    1989-01-01

    Sexual dysfunction takes place in the context of women's lives and affects their sexuality and self-esteem. Awareness of these influences are vital to the management of the dysfunction and the promotion of positive sexuality. The family physician's contribution to both the prevention and management of sexual concerns includes an awareness of societal influences and facilitation of a woman's sense of her own power and control over her life. PMID:21248971

  16. Novel Extracorporeal Therapies for Combined Renal-Pulmonary Dysfunction.

    PubMed

    Romagnoli, Stefano; Ricci, Zaccaria; Ronco, Claudio

    2016-01-01

    In modern intensive care medicine, lungs and kidneys frequently are involved in the context of multiorgan failure. When organ dysfunction occurs, the primary clinical management of critically ill patients is based on support/replacement of organ function until recovery. Mechanical ventilation is the first-line intervention in case of respiratory failure, but in most severe cases may, itself, cause ventilator-induced lung injury. The same inflammatory mechanism also may harm the kidney through mediator spillover from the injured lungs into the bloodstream. To limit the deleterious effects of mechanical ventilation and avoid excessive carbon dioxide accumulation, devices for extracorporeal CO2 removal (ECCO2R), have been developed. Some consistent clinical experience currently has been reached in patients with obstructive pulmonary disease and acute respiratory distress syndrome. Interestingly, ECCO2R recently has been coupled with continuous renal replacement therapy systems into specific lung-renal support. The results from the first experimental and clinical applications are encouraging: it is expected that a system including continuous renal replacement therapy and ECCO2R will develop from the current pioneering attempts into a feasible multiple-organ support platform to become commonly used as a routine tool in intensive care units. This review focuses on recent literature and clinical applications of renal-pulmonary support with specific attention to technical aspects of the most recent materials and devices.

  17. Mitochondrial Dysfunction in Depression

    PubMed Central

    Bansal, Yashika; Kuhad, Anurag

    2016-01-01

    Abstract: Background Depression is the most debilitating neuropsychiatric disorder with significant impact on socio-occupational and well being of individual. The exact pathophysiology of depression is still enigmatic though various theories have been put forwarded. There are evidences showing that mitochondrial dysfunction in various brain regions is associated with depression. Recent findings have sparked renewed appreciation for the role of mitochondria in many intracellular processes coupled to synaptic plasticity and cellular resilience. New insights in depression pathophysiology are revolving around the impairment of neuroplasticity. Mitochondria have potential role in ATP production, intracellular Ca2+ signalling to establish membrane stability, reactive oxygen species (ROS) balance and to execute the complex processes of neurotransmission and plasticity. So understanding the various concepts of mitochondrial dysfunction in pathogenesis of depression indubitably helps to generate novel and more targeted therapeutic approaches for depression treatment. Objective The review was aimed to give a comprehensive insight on role of mitochondrial dysfunction in depression. Result Targeting mitochondrial dysfunction and enhancing the mitochondrial functions might act as potential target for the treatment of depression. Conclusion Literature cited in this review highly supports the role of mitochondrial dysfunction in depression. As impairment in the mitochondrial functions lead to the generation of various insults that exaggerate the pathogenesis of depression. So, it is useful to study mitochondrial dysfunction in relation to mood disorders, synaptic plasticity, neurogenesis and enhancing the functions of mitochondria might show promiscuous effects in the treatment of depressed patients. PMID:26923778

  18. Telomere dysfunction induces metabolic and mitochondrial compromise

    PubMed Central

    Sahin, Ergün; Colla, Simona; Liesa, Marc; Moslehi, Javid; Müller, Florian L.; Guo, Mira; Cooper, Marcus; Kotton, Darrell; Fabian, Attila J.; Walkey, Carl; Maser, Richard S.; Tonon, Giovanni; Foerster, Friedrich; Xiong, Robert; Wang, Y. Alan; Shukla, Sachet A.; Jaskelioff, Mariela; Martin, Eric S.; Heffernan, Timothy P.; Protopopov, Alexei; Ivanova, Elena; Mahoney, John E.; Kost-Alimova, Maria; Perry, Samuel R.; Bronson, Roderick; Liao, Ronglih; Mulligan, Richard; Shirihai, Orian S.; Chin, Lynda; DePinho, Ronald A.

    2013-01-01

    Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and functional decline in high-turnover tissues. The broader adverse impact of telomere dysfunction across many tissues including more quiescent systems prompted transcriptomic network analyses to identify common mechanisms operative in haematopoietic stem cells, heart and liver. These unbiased studies revealed profound repression of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha and beta (PGC-1α and PGC-1β, also known as Ppargc1a and Ppargc1b, respectively) and the downstream network in mice null for either telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes. Consistent with PGCs as master regulators of mitochondrial physiology and metabolism, telomere dysfunction is associated with impaired mitochondrial biogenesis and function, decreased gluconeogenesis, cardiomyopathy, and increased reactive oxygen species. In the setting of telomere dysfunction, enforced Tert or PGC-1α expression or germline deletion of p53 (also known as Trp53) substantially restores PGC network expression, mitochondrial respiration, cardiac function and gluconeogenesis. We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1α and PGC-1β promoters, thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere–p53–PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction. PMID:21307849

  19. Delayed neutralization of interleukin 6 reduces organ injury, selectively suppresses inflammatory mediator, and partially normalizes immune dysfunction following trauma and hemorrhagic shock.

    PubMed

    Zhang, Yong; Zhang, Jinxiang; Korff, Sebastian; Ayoob, Faez; Vodovotz, Yoram; Billiar, Timothy R

    2014-09-01

    An excessive and uncontrolled systemic inflammatory response is associated with organ failure, immunodepression, and increased susceptibility to nosocomial infection following trauma. Interleukin 6 (IL-6) plays a particularly prominent role in the host immune response after trauma with hemorrhage. However, as a result of its pleiotropic functions, the effect of IL-6 in trauma and hemorrhage is still controversial. It remains unclear whether suppression of IL-6 after hemorrhagic shock and trauma will attenuate organ injury and immunosuppression. In this study, C57BL/6 mice were treated with anti-mouse IL-6 monoclonal antibody immediately prior to resuscitation in an experimental model combining hemorrhagic shock and lower-extremity injury. Interleukin 6 levels and signaling were transiently suppressed following administrations of anti-IL-6 monoclonal antibody following hemorrhagic shock and lower-extremity injury. This resulted in reduced lung and liver injury, as well as suppression in the levels of key inflammatory mediators including IL-10, keratinocyte-derived chemokine, monocyte chemoattractant protein 1, and macrophage inhibitory protein 1α at both 6 and 24 h. Furthermore, the shift to TH2 cytokine production and suppressed lymphocyte response were partly prevented. These results demonstrate that IL-6 is not only a biomarker but also an important driver of injury-induced inflammation and immune suppression in mice. Rapid measurement of IL-6 levels in the early phase of postinjury care could be used to guide IL-6-based interventions.

  20. Rare Presentation of Lupus Myocarditis With Acute Heart Failure-A Case Report.

    PubMed

    Malhotra, Gurveen; Chua, Serafin; Kodumuri, Vamsi; Sivaraman, Sivashankar; Ramdass, Priya

    Systemic lupus erythematosus is an autoimmune disease with diffuse organ involvement. The cardiac complications include pericarditis, myocarditis, pulmonary hypertension, coronary vasculitis, and Libman-Sacks endocarditis. Symptomatic lupus myocarditis presenting with left ventricular dysfunction, acute heart failure, and pulmonary edema, although rare, is a life-threatening complication. We report the occurrence of acute lupus myocarditis in a 38-year-old postpartum female who had a cesarean section a week before presentation for preeclampsia. Initially she was managed for pneumonia but later found to have acute pericarditis and myocarditis related to systemic lupus erythematosus. She had a complicated hospital course including acute respiratory failure and cardiogenic shock. She was started on pulse dose steroids besides the treatment for heart failure and had a dramatic improvement within days.

  1. Respiratory muscle dysfunction in facioscapulohumeral muscular dystrophy.

    PubMed

    Santos, Dante Brasil; Boussaid, Ghilas; Stojkovic, Tanya; Orlikowski, David; Letilly, Nadege; Behin, Anthony; Butel, Sandrine; Lofaso, Frédéric; Prigent, Hélène

    2015-08-01

    Respiratory insufficiency in facioscapulohumeral muscular dystrophy has rarely been studied. We compared two age- and sex-matched groups of 29 patients, with and without respiratory dysfunction. Tests in the 29 patients with respiratory dysfunction suggested predominant expiratory muscle dysfunction, leading to ineffective cough in 17 patients. Supine and upright vital capacities were not different (P = 0.76), suggesting absence of diaphragmatic dysfunction. By stepwise regression, only expiratory reserve volume correlated with the Walton and Gardner-Medwin score (R(2) = 0.503; P = 0.001). Compared to controls, patients with respiratory dysfunction had higher values for the Walton and Gardner-Medwin score (6.1 ± 1.9 vs. 3.2 ± 1.2; P <0.0001) and body mass index (26.9 ± 6.0 vs. 22.9 ± 4.0 kg/m(2); P = 0.003) and a smaller number of D4Z4 allele repeats (4.8 ± 1.6 vs. 5.7 ± 1.8; P = 0.05). Mechanical ventilation was required eventually in 20 patients, including 14 who were wheelchair bound. Three patients had acute respiratory failure requiring mechanical ventilation; 16 patients had poor airway clearance, including 10 with sleep apnea syndrome, responsible in 7 for chronic hypercapnia. Two patients presented isolated severe sleep apnea syndrome. Respiratory dysfunction in facioscapulohumeral muscular dystrophy is predominantly related to expiratory muscle weakness. Respiratory function and cough effectiveness should especially be monitored in patients with severe motor impairment and high body mass index.

  2. Acute consumption of organic and conventional tropical grape juices (Vitis labrusca L.) increases antioxidants in plasma and erythrocytes, but not glucose and uric acid levels, in healthy individuals.

    PubMed

    Toaldo, Isabela Maia; Cruz, Fernanda Alves; da Silva, Edson Luiz; Bordignon-Luiz, Marilde T

    2016-08-01

    Bioactive polyphenols in grapes are influenced by grape variety and cultivation conditions. The Vitis labrusca L. varieties are cultivated in tropical regions and used for grape juice production. We hypothesized that polyphenols from tropical grape juices would beneficially affect redox homeostasis in humans. Therefore, the effects of acute consumption of organic and conventional grape juices from V labrusca L. on antioxidants biomarkers were investigated in healthy individuals. In a controlled, randomized, crossover, intervention trial, 24 individuals were assigned to drink 400 mL of conventional juice, organic juice, or water. Each intervention was followed by a 14-day washout period. Blood samples were obtained before and 1 hour after acute intake and analyzed for erythrocyte reduced glutathione, serum total antioxidant capacity, antioxidant enzymes in erythrocytes, and glucose and uric acid in serum. The ingestion of both grape juices resulted in elevated levels of reduced glutathione (P< .001) and serum total antioxidant capacity (P< .05) and increased activity of catalase (P< .001), superoxide dismutase (P< .001), and glutathione peroxidase (P< .05) compared with the control intervention, with no significant differences between grape juices (P< .05). The intake of juices did not affect significantly the concentrations of glucose or uric acid. Grape juice polyphenols were associated with increased antioxidants, and the chemical differences between organic and conventional juices were not predictive of the observed responses. The results suggest a bioactive potential of V labrusca L. juices to improve redox homeostasis, which is involved in defense against oxidative stress in humans.

  3. Uncoupled Cardiac Nitric Oxide Synthase Mediates Diastolic Dysfunction

    PubMed Central

    Silberman, Gad A.; Fan, Tai-Hwang M.; Liu, Hong; Jiao, Zhe; Xiao, Hong D.; Lovelock, Joshua D.; Boulden, Beth M.; Widder, Julian; Fredd, Scott; Bernstein, Kenneth E.; Wolska, Beata M.; Dikalov, Sergey; Harrison, David G.; Dudley, Samuel C.

    2010-01-01

    Background Heart failure with preserved ejection fraction is one consequence of hypertension and caused by impaired cardiac diastolic relaxation. Nitric oxide (NO) is a known modulator of cardiac relaxation. Hypertension can lead to a reduction in vascular NO, in part because nitric oxide synthase (NOS) becomes uncoupled when oxidative depletion of its co-factor tetrahydrobiopterin (BH4) occurs.Similar events may occur in the heart leading to uncoupled NOS and diastolic dysfunction. Methods and Results In a hypertensive mouse model, diastolic dysfunction was accompanied by cardiac oxidation, a reduction in cardiac BH4, and uncoupled NOS. Compared to sham-operated animals, male mice with unilateral nephrectomy, with subcutaneous implantation of a controlled release deoxycorticosterone acetate (DOCA) pellet, and given 1% saline to drink were mildly hypertensive and had diastolic dysfunction in the absence of systolic dysfunction or cardiac hypertrophy. The hypertensive mouse hearts showed increased oxidized biopterins, NOS-dependent superoxide production, reduced NO production, and phosphorylated phospholamban. Feeding hypertensive mice BH4 (5 mg/day), but not treating with hydralazine or tetrahydroneopterin, improved cardiac BH4 stores, phosphorylated phospholamban levels, and diastolic dysfunction. Isolated cardiomyocyte experiments revealed impaired relaxation that was normalized with acute BH4 treatment. Targeted cardiac overexpression of angiotensin converting enzyme also resulted in cardiac oxidation, NOS uncoupling, and diastolic dysfunction in the absence of hypertension. Conclusions Cardiac oxidation, independent of vascular changes, can lead to uncoupled cardiac NOS and diastolic dysfunction. BH4 may represent a possible treatment for diastolic dysfunction. PMID:20083682

  4. Oxidative stress and mitochondrial dysfunction in sepsis.

    PubMed

    Galley, H F

    2011-07-01

    Sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit (ICU), despite advances in healthcare and science. Marked oxidative stress as a result of the inflammatory responses inherent with sepsis initiates changes in mitochondrial function which may result in organ damage. Normally, a complex system of interacting antioxidant defences is able to combat oxidative stress and prevents damage to mitochondria. Despite the accepted role that oxidative stress-mediated injury plays in the development of organ failure, there is still little conclusive evidence of any beneficial effect of systemic antioxidant supplementation in patients with sepsis and organ dysfunction. It has been suggested, however, that antioxidant therapy delivered specifically to mitochondria may be useful.

  5. Adolescent Depression: Stress and Reward Dysfunction

    PubMed Central

    Auerbach, Randy P.; Admon, Roee; Pizzagalli, Diego A.

    2014-01-01

    Adolescence is a peak period for the onset of depression, and it is also a time marked by substantial stress as well as neural development within the brain reward circuitry. In the current review, we provide a selective overview of current animal and human research investigating the relationship among reward processes, stress, and depression. Three separate, but related, etiological models examine the differential roles that stress may play with regard to reward dysfunction and adolescent depression. First, the reward mediation model suggests that acute and chronic stress contribute to reward deficits, which in turn, potentiate depressive symptoms and/or increase the risk for depression. Second, in line with the stress generation perspective, it is plausible that premorbid reward-related dysfunction generates stress, in particular interpersonal stress, which then leads to the manifestation of depressive symptoms. Last, consistent with a diathesis-stress model, the interaction between stress and premorbid reward dysfunction may contribute to the onset of depression. Given the equifinal nature of depression, these models could shed important light on different etiological pathways during adolescence, particularly as they may relate to understanding the heterogeneity of depression. To highlight the translational potential of these insights, a hypothetical case study is provided as means of demonstrating the importance of targeting reward dysfunction in both assessment and treatment of adolescent depression. PMID:24704785

  6. Endothelial dysfunction: a comprehensive appraisal

    PubMed Central

    Esper, Ricardo J; Nordaby, Roberto A; Vilariño, Jorge O; Paragano, Antonio; Cacharrón, José L; Machado, Rogelio A

    2006-01-01

    The endothelium is a thin monocelular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease. There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the vasodilatation produced by drugs that

  7. Sunlight-driven reduction of silver ion to silver nanoparticle by organic matter mitigates the acute toxicity of silver to Daphnia magna.

    PubMed

    Zhang, Zhen; Yang, Xiaoya; Shen, Mohai; Yin, Yongguang; Liu, Jingfu

    2015-09-01

    Due to the unique antibacterial activities, silver nanoparticles (AgNPs) have been extensively used in commercial products. Anthropogenic activities have released considerable AgNPs as well as highly toxic silver ion (Ag(+)) into the aquatic environment. Our recent study revealed that ubiquitous natural organic matter (NOM) could reduce Ag(+) to AgNP under natural sunlight. However, the toxic effect of this process is not well understood. In this work, we prepared mixture solution of Ag(+) and AgNPs with varied Ag(+)% through the sunlight-driven reduction of Ag(+) by NOM and investigated the acute toxicity of the solutions on Daphnia magna. Formation of AgNPs was demonstrated and characterized by comprehensive techniques and the fraction of unconverted Ag(+) was determined by ultrafiltration-inductively coupled plasma mass spectrometry determination. The formation of AgNPs enhanced significantly with the increasing of solution pH and cumulative photosynthetically active radiation of sunlight. The toxicity of the resulting solution was further investigated by using freshwater crustacean D. magna as a model and an 8hr-median lethal concentration (LC50) demonstrated that the reduction of Ag(+) by NOM to AgNPs significantly mitigated the acute toxicity of silver. These results highlight the importance of sunlight and NOM in the fate, transformation and toxicity of Ag(+) and AgNPs, and further indicate that the acute toxicity of AgNPs should be mainly ascribed to the dissolved Ag(+) from AgNPs.

  8. Deciphering the complexity of acute inflammation using mathematical models.

    PubMed

    Vodovotz, Yoram

    2006-01-01

    Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. The EBMs describe and predict various features of septic shock and trauma/hemorrhage (including the response to anthrax, preconditioning phenomena, and irreversible hemorrhage) and were used to simulate anti-inflammatory strategies in clinical trials. The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.

  9. Comparison of the usefulness of Doppler-derived deceleration time versus plasma brain natriuretic peptide to predict left ventricular remodeling after mechanical revascularization in patients with ST-elevation acute myocardial infarction and left ventricular systolic dysfunction.

    PubMed

    Cerisano, Giampaolo; Pucci, Paolo Domenico; Valenti, Renato; Boddi, Vieri; Migliorini, Angela; Tommasi, Maria Silvia; Raspanti, Silvia; Parodi, Guido; Antoniucci, David

    2005-04-15

    The correlation between Doppler deceleration time (DT) and brain natriuretic peptide (BNP) and their predictive value for detecting left ventricular (LV) remodeling in patients who are treated with primary percutaneous intervention for infarction and LV dysfunction are unknown. Fifty-six patients (64 +/- 12 years of age; 11 women) who had a first ST-segment elevation myocardial infarction and systolic dysfunction that was successfully treated with direct primary coronary intervention underwent 2-dimensional Doppler echocardiographic and plasma BNP evaluation at days 1 and 3 and 1 and 6 months after the index infarction. Repeat coronary angiograms were obtained at 1 and 6 months. Because of previous consistent evidence, 3 days after the index infarction was the time point of comparison between BNP and DT values. Echocardiographic LV remodeling was defined as an increase in end-diastolic volume index above baseline values of 2 x SD. Ventricular remodeling occurred in 20 patients (36%). Multivariate analyses that included BNP level, Doppler DT, echocardiographic measurements of systolic function, peak creatine kinase, and anterior infarct location showed Doppler DT to be the only predictor of LV remodeling (odds ratio 0.963, 95% confidence interval 0.936 to 0.990, p = 0.008). The optimal cutoff for DT in the prediction of 6-month LV remodeling was <136 ms (sensitivity 75%, specificity 97%, accuracy 81%, area under receiver-operating characteristic curve 0.90). Thus, in patients who have a first ST-segment elevation myocardial infarction and LV systolic dysfunction that is successfully treated with primary percutaneous coronary intervention, Doppler-derived DT 3 days after index infarction is more effective than BNP level in detecting patients who are at higher risk for 6-month LV remodeling.

  10. Sepsis and Acute Kidney Injury.

    PubMed

    Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

    2014-12-01

    Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.

  11. Sepsis and Acute Kidney Injury

    PubMed Central

    Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

    2014-01-01

    Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically “Risk-Injury-Failure-Loss-Endstage” (RIFLE), “Acute Kidney Injury Netwok” (AKIN) and “The Kidney Disease/ Improving Global Outcomes” (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also “cell cycle arrest” molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated. PMID:27366441

  12. Diastolic dysfunction in hypertension.

    PubMed

    Nazário Leão, R; Marques da Silva, P

    2017-03-03

    Hypertension and coronary heart disease, often coexisting, are the most common risk factors for heart failure. The progression of hypertensive heart disease involves myocardial fibrosis and alterations in the left ventricular geometry that precede the functional change, initially asymptomatic. The left ventricular diastolic dysfunction is part of this continuum being defined by the presence of left ventricular diastolic dysfunction without signs or symptoms of heart failure or poor left ventricular systolic function. It is highly prevalent in hypertensive patients and is associated with increased cardiovascular morbidity and mortality. Despite its growing importance in clinical practice it remains poorly understood. This review aims to present the epidemiological fundamentals and the latest developments in the pathophysiology, diagnosis and treatment of left ventricular diastolic dysfunction.

  13. Cardiac dysfunctions following spinal cord injury

    PubMed Central

    Sandu, AM; Popescu, M; Iacobini, MA; Stoian, R; Neascu, C; Popa, F

    2009-01-01

    The aim of this article is to analyze cardiac dysfunctions occurring after spinal cord injury (SCI). Cardiac dysfunctions are common complications following SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. We reviewed epidemiology of cardiac disturbances after SCI, and neuroanatomy and pathophysiology of autonomic nervous system, sympathetic and parasympathetic. SCI causes disruption of descendent pathways from central control centers to spinal sympathetic neurons, originating into intermediolateral nuclei of T1–L2 spinal cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant cardiac dysfunction. Impairment of autonomic nervous control system, mostly in patients with cervical or high thoracic SCI, causes cardiac dysrrhythmias, especially bradycardia and, rarely, cardiac arrest, or tachyarrhytmias and hypotension. Specific complication dependent on the period of time after trauma like spinal shock and autonomic dysreflexia are also reviewed. Spinal shock occurs during the acute phase following SCI and is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe bradycardia and hypotension. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Besides all this, additional cardiac complications, such as cardiac deconditioning and coronary heart disease may also occur. Proper prophylaxis, including nonpharmacologic and pharmacological strategies and cardiac rehabilitation diminish occurrence of the cardiac dysfunction following

  14. Acute toxicity of smoke screen materials to aquatic organisms, white phosphorus-felt, red phosphorus-butyl rubber and SGF No. 2 fog oil. Final report

    SciTech Connect

    Poston, T.M.; McFadden, K.M.; Bean, R.M.; Clark, M.L.; Thomas, B.L.; Killand, B.W.; Prohammer, L.A.; Kalkwarf, D.R.

    1986-04-01

    The acute toxicity of three obscurants was determined for nine freshwater organisms. The materials tested were white phosphorus-felt smoke, red phosphorus-butyl rubber (RP-BR) smoke, and smoke generator fuel (SGF) No. 2 fog oil (bulk and vaporized). The chemistry of WP-F and RP-BR smoke in water and the resulting effects on aquatic organisms are similar. Combustion of these two obscurants and their deposition in water leads to the formation of many complex oxy-phosphoric acids. Rates of hydrolysis of these complex products to ortho-phosphate were inconsistent and unpredictable over time. These products acidify water and produce toxic effects after exhausting the buffering capacity of the water. Acute 96 hr tests using Daphnia magna with neutralized and nonneutralized exposure solutions indicated that the presence of unidentified toxic component(s) acted independently of pH. At pH levels of 6.0 to 7.0, phosphorus combustion products precipitated out of solution leading to a bimodal toxic response in extended 96-hr tests with Daphnia magna. Most components of fog oil had low solubility in water. Saturation was apparent at approximately 0.1 to 0.3 mg/L total oil. Vaporization had no demonstrable effect on the chemistry or toxicity of the fog oil. Neither the bulk fog oil nor the vaporized fog oil was acutely toxic to freshwater animals at concentrations less than 10 mg/L total oil. In oil-water mixes in excess of 1.0 mg/L total oil, fog oil quickly separated and floated to the surface. The primary hazard associated with vaporized and bulk fog oil was the physical effect of oil fouling the organisms. Photolysis increased the concentration of water-soluble components of the fog oil. Acute toxicity was demonstrated in oil-water mixes (approx.10 mg/L total oil) of photolyzed bulk and vaporized fog oil. No difference in toxicity was observed between photolyzed and non-photolyzed dilutions of OWM at comparable levels of total oil.

  15. Toxicity of TNT Wastewaters to Aquatic Organisms. Volume 1. Acute Toxicity of LAP Wastewater and 2,4,6-Trinitrotoluene

    DTIC Science & Technology

    1983-03-01

    used to assess the adequacy of current pollution abatement technologies and thus influence research and development in this area. This report...wastewater samples, was defined as a 1.6-to-I mixture o! TNT and RDX. "The results of flow-through acute toxicity terzs with the inverte - brate Daphniamagna...The "unadjusted" confidence interval for the LCSO is derived by inverting the likelihood ratio test for determining whether any specified

  16. DELAYED EFFECTS OF ACUTE RADIATION EXPOSURE IN A MURINE MODEL OF THE H-ARS: MULTIPLE-ORGAN INJURY CONSEQUENT TO <10 GY TOTAL BODY IRRADIATION

    PubMed Central

    Unthank, Joseph L.; Miller, Steven J.; Quickery, Ariel K.; Ferguson, Ethan L.; Wang, Meijing; Sampson, Carol H.; Chua, Hui Lin; DiStasi, Matthew R.; Feng, Hailin; Fisher, Alexa; Katz, Barry P.; Plett, P. Artur; Sandusky, George E.; Sellamuthu, Rajendran; Vemula, Sasidhar; Cohen, Eric P.; MacVittie, Thomas J.; Orschell, Christie M.

    2015-01-01

    The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a 137Cs radiation source and studied 1–21 months later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ~22 to 34 ± 3.8 and 69±6.0 mg/dl, p<0.01 vs non-irradiated controls) and correlated with glomerosclerosis (29±1.8% vs 64±9.7% of total glomeruli, p<0.01 vs non-irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peri-bronchial fibrosis/collagen deposition was observed from ~9–21 mo post-TBI in kidney, heart and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs. PMID:26425910

  17. Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation.

    PubMed

    Unthank, Joseph L; Miller, Steven J; Quickery, Ariel K; Ferguson, Ethan L; Wang, Meijing; Sampson, Carol H; Chua, Hui Lin; DiStasi, Matthew R; Feng, Hailin; Fisher, Alexa; Katz, Barry P; Plett, P Artur; Sandusky, George E; Sellamuthu, Rajendran; Vemula, Sasidhar; Cohen, Eric P; MacVittie, Thomas J; Orschell, Christie M

    2015-11-01

    The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p < 0.01 vs. non-irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p < 0.01 vs. non-irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs.

  18. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis

    PubMed Central

    Gimbrone, Michael A.; García-Cardeña, Guillermo

    2016-01-01

    Dysfunction of the endothelial lining of lesion-prone areas of the arterial vasculature is an important contributor to the pathobiology of atherosclerotic cardiovascular disease. Endothelial cell dysfunction (ECD), in its broadest sense, encompasses a constellation of various non-adaptive alterations in functional phenotype, which have important implications for the regulation of hemostasis and thrombosis, local vascular tone and redox balance, and the orchestration of acute and chronic inflammatory reactions within the arterial wall. In this review, we trace the evolution of the concept of endothelial cell dysfunction, focusing on recent insights into the cellular and molecular mechanisms that underlie its pivotal roles in atherosclerotic lesion initiation and progression; explore its relationship to classic, as well as more recently defined, clinical risk factors for atherosclerotic cardiovascular disease; consider current approaches to the clinical assessment of endothelial cell dysfunction; and outline some promising new directions for its early detection and treatment. PMID:26892962

  19. [Recurrent pancreatitis secondary to sphincter of Oddi dysfunction: case report].

    PubMed

    Calzadilla, Jeannette; Sanhueza, Natalia; Farías, Solange; González, Félix

    2016-10-21

    Dysfunction of the sphincter of Oddi is a rare disease that causes about 20% of recurrent idiopathic pancreatitis. In order to suspect its existence, it is mandatory to have ruled out all other causes of acute pancreatitis. Then, the disease needs to be classified by degree of dysfunction and have a manometry performed as it is considered the gold standard of diagnosis. Manometry is used to guide treatment and its method of choice is usually an endoscopic sphincterotomy. In this article a case of recurrent pancreatitis is discussed, which after a thorough study that ruled out other etiologies, was diagnosed as a pancreatic-type dysfunction of the sphincter of Oddi. The dysfunction was resolved by endoscopic sphincterotomy and the patient had a favorable course without any recurrence of symptoms.

  20. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome.

    PubMed

    Bhatia, Madhav; Moochhala, Shabbir

    2004-02-01

    Inflammatory response leading to organ dysfunction and failure continues to be the major problem after injury in many clinical conditions such as sepsis, severe burns, acute pancreatitis, haemorrhagic shock, and trauma. In general terms, systemic inflammatory response syndrome (SIRS) is an entirely normal response to injury. Systemic leukocyte activation, however, is a direct consequence of a SIRS and if excessive, can lead to distant organ damage and multiple organ dysfunction syndrome (MODS). When SIRS leads to MODS and organ failure, the mortality becomes high and can be more than 50%. Acute lung injury that clinically manifests as acute respiratory distress syndrome (ARDS) is a major component of MODS of various aetiologies. Inflammatory mediators play a key role in the pathogenesis of ARDS, which is the primary cause of death in these conditions. This review summarizes recent studies that demonstrate the critical role played by inflammatory mediators such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, platelet activating factor (PAF), IL-10, granulocyte macrophage-colony stimulating factor (GM-CSF), C5a, intercellular adhesion molecule (ICAM)-1, substance P, chemokines, VEGF, IGF-I, KGF, reactive oxygen species (ROS), and reactive nitrogen species (RNS) in the pathogenesis of ARDS. It is reasonable to speculate that elucidation of the key mediators in ARDS coupled with the discovery of specific inhibitors would make it possible to develop clinically effective anti-inflammatory therapy.

  1. Adipocytokines in Thyroid Dysfunction

    PubMed Central

    Aydogan, Berna İmge; Sahin, Mustafa

    2013-01-01

    Adipocytokines are important mediators of interorgan crosstalk in metabolic regulation. Thyroid diseases have effects on metabolism and inflammation. The mechanism of these effects is not clear. Recently, there are several reports suggesting this interrelation between adipocytokines and thyroid dysfunction. In this review, we summarize this relation according to the literature. PMID:24049662

  2. Perceptual-Motor Dysfunction.

    ERIC Educational Resources Information Center

    Pyfer, Jean L.

    Discussed are theoretical and treatment aspects of perceptual motor dysfunction and rehabilitation in 4- to 12-year-old academically failing children involved in a 3-year investigation at the University of Kansas. The program is said to stress increasing the amount of stimulation received by sensory receptors of the vestibular, reflex, and haptic…

  3. Female sexual dysfunction: Assessment.

    PubMed

    Sharma, J B; Kalra, Bharti

    2016-05-01

    Female sexual dysfunction (FSD) is a common complex clinical condition, with multiple etiologies, association and pathophysiologic correlations. This review includes the definition, etiology, and diagnosis of FSD. It calls for a bio psychosocial approach to FSD management, which incorporates, but is not limited to, only the psychological aspects of FSD.

  4. Female Sexual Dysfunction

    MedlinePlus

    ... on women with certain sexual dysfunctions, but more study is needed. Yoga. During yoga, you perform a series of postures and controlled breathing exercises to promote a flexible body and a calm mind. Certain subsets of yoga aim to channel the ...

  5. Shared Parenting Dysfunction.

    ERIC Educational Resources Information Center

    Turkat, Ira Daniel

    2002-01-01

    Joint custody of children is the most prevalent court ordered arrangement for families of divorce. A growing body of literature indicates that many parents engage in behaviors that are incompatible with shared parenting. This article provides specific criteria for a definition of the Shared Parenting Dysfunction. Clinical aspects of the phenomenon…

  6. Parallel comparison of risk factors between progression of organic stenosis in the coronary arteries and onset of acute coronary syndrome by covariance structure analysis

    PubMed Central

    Ogawa, Kazuo; Minai, Kosuke; Kawai, Makoto; Tanaka, Toshikazu; Nagoshi, Tomohisa; Ogawa, Takayuki; Yoshimura, Michihiro

    2017-01-01

    Background It is widely accepted that progression of organic stenosis in the coronary arteries and onset of acute coronary syndrome (ACS) are similar in the development of atherosclerosis. However, the extent of the association of each risk factor with the respective pathological conditions has not been fully elucidated. Objectives We investigated the differences in risk factors between these conditions using a statistical procedure. Methods The study population consisted of 1,029 patients with ischemic heart disease (IHD). We divided the study population into two groups (ACS and non-ACS) and by diseased vessels (organic stenosis). Covariance structure analysis was simultaneously performed in one equation model for determination and comparison of the risk factors for organic stenosis and ACS. Results The analysis revealed that age (standardized regression coefficient, β: 0.206, P < 0.001), male gender (β: 0.126, P < 0.001), HbA1c level (β: 0.109, P < 0.001), HDL level (β: -0.109, P < 0.001) and LDL level (β: 0.127, P = 0.002) were significant for the advancement of organic stenosis. HDL level (β: 0100, P = 0.002) and MDA-LDL level (β: 0.335, P < 0.001) were significant for the onset of ACS, but age, HbA1c and LDL (P = NS or β < 0.1, respectively) were not. Among the risk factors, age, HbA1c and LDL were significantly more strongly associated with organic stenosis than ACS, while MDA-LDL was significantly more strongly associated with ACS than organic stenosis. Conclusions The current statistical analysis revealed clear differences among the risk factors between the progression of organic stenosis and the onset of ACS. Among them, the MDA-LDL level should be considered to indicate a substantial risk of ACS. PMID:28301565

  7. Heart Rate Variability in Male Sexual Arousal and Erectile Dysfunction

    DTIC Science & Technology

    2007-01-22

    participants with organic ED. However, negative or distracting cognitions that could affect ANS activity were not accounted for in either study because...Physiology 1 a. The Autonomic Nervous System II. Erectile Dysfunction 5 a. ED from Organic Causes b. ED from Psychogenic...Medical Information i. Medical Information Form ii. Organicity /Psychogenic Rating Scale d. Physiological i. Penile Plethysmograph ii. Heart Rate II

  8. Making sense of multiple organ dysfunction syndrome.

    PubMed

    Krau, Stephen D

    2007-03-01

    Despite recent advances in critical care medicine, caring for patients with MODS remains one of the most challenging experience a critical care can encounter. New therapies that current exist and continue to be developed contribute to successful outcomes for patients with MODS, but there is no substitute for prevention and early intervention for persons at risk for developing MODS. Early and subtle changes in the patient who is at risk and has endured an initial insult can make a great difference in the patient's outcome and chances of mortality. Goal-directed therapy, supportive management, as well as an understanding of the inflammatory process are key to decreasing the mortality rate among patients with MODS.

  9. The neurologic manifestations of the acute porphyrias.

    PubMed

    Simon, Neil G; Herkes, Geoffrey K

    2011-09-01

    The porphyrias are diseases characterised by accumulation of porphyrins and porphyrin precursors owing to enzymatic deficiencies of the haem synthetic pathway. In the acute hepatic porphyrias accumulation of porphyrin precursors, in particular delta-aminolaevulinic acid (ALA), cause dysfunction of the central, peripheral and autonomic nervous systems. This leads to the characteristic clinical findings of abdominal pain, neuropsychiatric symptoms and neuropathy. The exact pathogenic mechanism is not clear but evidence to date suggests both direct toxic effects of ALA and intracellular metabolic derangement contribute to the neurologic disorders. This review explores the mechanisms of neural dysfunction in the acute porphyrias and the resultant clinical features of an acute attack.

  10. What Is a Dysfunctional School?

    ERIC Educational Resources Information Center

    Bergman, M. M.

    2013-01-01

    Whether or not a school is dysfunctional depends largely on how dysfunctionality in schools is defined and measured. Dysfunctionality, as any construct, is subject to definition and interpretation, and it is thus always marked by perspectivism. But regardless of the definition games occasionally played by academics, some form of reality takes…

  11. Organics.

    ERIC Educational Resources Information Center

    Chian, Edward S. K.; DeWalle, Foppe B.

    1978-01-01

    Presents water analysis literature for 1978. This review is concerned with organics, and it covers: (1) detergents and surfactants; (2) aliphatic and aromatic hydrocarbons; (3) pesticides and chlorinated hydrocarbons; and (4) naturally occurring organics. A list of 208 references is also presented. (HM)

  12. Organizers.

    ERIC Educational Resources Information Center

    Callison, Daniel

    2000-01-01

    Focuses on "organizers," tools or techniques that provide identification and classification along with possible relationships or connections among ideas, concepts, and issues. Discusses David Ausubel's research and ideas concerning advance organizers; the implications of Ausubel's theory to curriculum and teaching; "webbing," a…

  13. Prevalence of Sexual Dysfunctions

    PubMed Central

    Simons, Jeffrey; Carey, Michael P.

    2008-01-01

    Ten years of research that has provided data regarding the prevalence of sexual dysfunctions is reviewed. A thorough review of the literature identified 52 studies that have been published in the 10 years since an earlier review by Spector and Carey (1990). Community samples indicate a current prevalence of 0 - 3% for male orgasmic disorder, 0 - 5% for erectile disorder, and 0 - 3% for male hypoactive sexual desire disorder. Pooling current and 1-year figures provides community prevalence estimates of 7 - 10% for female orgasmic disorder and 4 - 5% for premature ejaculation. Stable community estimates of the current prevalence for the other sexual dysfunctions remain unavailable. Prevalence estimates obtained from primary care and sexuality clinic samples are characteristically higher. Although a relatively large number of studies have been conducted since Spector and Carey’s (1990) review, the lack of methodological rigor of many studies limits the confidence that can be placed in these findings. PMID:11329727

  14. The cone dysfunction syndromes

    PubMed Central

    Aboshiha, Jonathan; Dubis, Adam M; Hardcastle, Alison J; Michaelides, Michel

    2016-01-01

    The cone dysfunction syndromes are a heterogeneous group of inherited, predominantly stationary retinal disorders characterised by reduced central vision and varying degrees of colour vision abnormalities, nystagmus and photophobia. This review details the following conditions: complete and incomplete achromatopsia, blue-cone monochromatism, oligocone trichromacy, bradyopsia and Bornholm eye disease. We describe the clinical, psychophysical, electrophysiological and imaging findings that are characteristic to each condition in order to aid their accurate diagnosis, as well as highlight some classically held notions about these diseases that have come to be challenged over the recent years. The latest data regarding the genetic aetiology and pathological changes observed in the cone dysfunction syndromes are discussed, and, where relevant, translational avenues of research, including completed and anticipated interventional clinical trials, for some of the diseases described herein will be presented. Finally, we briefly review the current management of these disorders. PMID:25770143

  15. Sexual Dysfunction After Urethroplasty.

    PubMed

    Dogra, Prem Nath; Singh, Prabhjot; Nayyar, Rishi; Yadav, Siddharth

    2017-02-01

    Posturethroplasty sexual dysfunction (SD) is multifactorial and its true incidence is unknown. Even with the current evidence suggesting that it is uncommon, de novo SD causes dissatisfaction even after a successful surgery. Posterior urethroplasty carries the highest chance of SD, mostly attributable to the pelvic fracture itself rather than the urethroplasty. With anterior urethroplasty, transecting bulbar urethroplasty leads to greater SD compared with penile or nontransecting bulbar urethroplasty. Most patients with posturethroplasty SD recover within 6 months after surgery.

  16. Preclinical Diastolic Dysfunction

    PubMed Central

    Wan, Siu-Hin; Vogel, Mark W.; Chen, Horng H

    2014-01-01

    Preclinical Diastolic Dysfunction (PDD) has been broadly defined as subjects with left ventricular diastolic dysfunction, without the diagnosis of congestive heart failure (HF), and with normal systolic function. PDD is an entity which remains poorly understood, yet has definite clinical significance. Although few original studies have focused on PDD, it has been shown that PDD is prevalent, and that there is a clear progression from PDD to symptomatic heart failure including dyspnea, edema, and fatigue. In diabetic patients and patients with coronary artery disease or hypertension, it has been shown that patients with PDD have a significantly higher risk of progression to heart failure and death compared to patients without PDD. Because of these findings and the increasing prevalence of the heart failure epidemic, it is clear that an understanding of PDD is essential to decreasing patients’ morbidity and mortality. This review will focus on what is known concerning preclinical diastolic dysfunction, including definitions, staging, epidemiology, pathophysiology, and the natural history of the disease. In addition, given the paucity of trials focused on PDD treatment, studies targeting risk factors associated with the development of PDD and therapeutic trials for heart failure with preserved ejection fraction will be reviewed. PMID:24291270

  17. Volatile Organic Compound Gamma-Butyrolactone Released upon Herpes Simplex Virus Type -1 Acute Infection Modulated Membrane Potential and Repressed Viral Infection in Human Neuron-Like Cells

    PubMed Central

    Waguespack, Yan; Figliozzi, Robert W.; Kharel, Madan K.; Zhang, Qiaojuan; Martin-Caraballo, Miguel

    2016-01-01

    Herpes Simplex Virus Type -1 (HSV-1) infections can cause serious complications such as keratitis and encephalitis. The goal of this study was to identify any changes in the concentrations of volatile organic compounds (VOCs) produced during HSV-1 infection of epithelial cells that could potentially be used as an indicator of a response to stress. An additional objective was to study if any VOCs released from acute epithelial infection may influence subsequent neuronal infection to facilitate latency. To investigate these hypotheses, Vero cells were infected with HSV-1 and the emission of VOCs was analyzed using two-dimensional gas chromatograph/mass spectrometry (2D GC/MS). It was observed that the concentrations of gamma-butyrolactone (GBL) in particular changed significantly after a 24-hour infection. Since HSV-1 may establish latency in neurons after the acute infection, GBL was tested to determine if it exerts neuronal regulation of infection. The results indicated that GBL altered the resting membrane potential of differentiated LNCaP cells and promoted a non-permissive state of HSV-1 infection by repressing viral replication. These observations may provide useful clues towards understanding the complex signaling pathways that occur during the HSV-1 primary infection and establishment of viral latency. PMID:27537375

  18. Endogenous Il10 alleviates the systemic antiviral cellular immune response and T cell-mediated immunopathology in select organs of acutely LCMV-infected mice.

    PubMed

    Jakobshagen, Kristin; Ward, Beate; Baschuk, Nikola; Huss, Sebastian; Brunn, Anna; Malecki, Monika; Fiolka, Michael; Rappl, Gunther; Corogeanu, Diana; Karow, Ulrike; Schiller, Petra; Abken, Hinrich; Heukamp, Lukas C; Deckert, Martina; Krönke, Martin; Utermöhlen, Olaf

    2015-11-01

    The immunoregulatory cytokine IL-10 suppresses T-cell immunity. The complementary question, whether IL-10 is also involved in limiting the collateral damage of vigorous T cell responses, has not been addressed in detail. Here, we report that the particularly strong virus-specific immune response during acute primary infection with the lymphocytic choriomeningitis virus (LCMV) in mice is significantly further increased in Il10-deficient mice, particularly regarding frequencies and cytotoxic activity of CD8(+) T cells. This increase results in exacerbating immunopathology in select organs, ranging from transient local swelling to an increased risk for mortality. Remarkably, LCMV-induced, T cell-mediated hepatitis is not affected by endogenous Il10. The alleviating effect of Il10 on LCMV-induced immunopathology was found to be operative in delayed-type hypersensitivity footpad-swelling reaction and in debilitating meningitis in mice of both the C57BL/6 and BALB/c strains. These strains are prototypic counterpoles for genetically imprinted type 1-biased versus type 2-biased T cell-mediated immune responses against various infectious pathogens. However, during acute LCMV infection, neither systemic cytokine patterns nor the impact of Il10 on LCMV-induced immunopathology differed conspicuously between these two strains of mice. This study documents a physiological role of Il10 in the regulation of a balanced T-cell response limiting immunopathological damage.

  19. Sexual dysfunction with antihypertensive drugs.

    PubMed

    Prisant, L M; Carr, A A; Bottini, P B; Solursh, D S; Solursh, L P

    1994-04-11

    The relationship of antihypertensive drugs have a long history of association with sexual dysfunction; however, this relationship is poorly documented. There appears to be a higher rate of sexual dysfunction in untreated hypertensive men compared with normotensive men. Sexual dysfunction increases with age and is associated with physical and emotional symptoms. There are few studies assessing sexual dysfunction with female and African-American hypertensive patients. Sexual dysfunction is associated with impairment of quality of life and noncompliance. Since group data may hide individual drug effects, baseline data should be collected on all patients before initiating therapy with any antihypertensive agent. Although questionnaires may not provide objective information on sexual dysfunction, the response rate to direct questioning may be less than the response rate on a questionnaire and may be affected by the gender or race of the interviewer. Research protocols using a double-blind, placebo-controlled design should assess sexual dysfunction in men and women in a standardized fashion.

  20. The Different Effects of BMI and WC on Organ Damage in Patients from a Cardiac Rehabilitation Program after Acute Coronary Syndrome

    PubMed Central

    Xu, Lin; Zhao, Hui; Qiu, Jian; Zhu, Wei; Lei, Hongqiang; Cai, Zekun; Lin, Wan-Hua; Huang, Wenhua; Zhang, Heye; Zhang, Yuan-Ting

    2015-01-01

    One of the purposes of cardiac rehabilitation (CR) after acute coronary syndrome (ACS) is to monitor and control weight of the patient. Our study is to compare the different obesity indexes, body mass index (BMI), and waist circumference (WC), through one well-designed CR program (CRP) with ACS in Guangzhou city of Guangdong Province, China, in order to identify different effects of BMI and WC on organ damage. In our work, sixty-one patients between October 2013 and January 2014 fulfilled our study. We collected the vital signs by medical records, the clinical variables of body-metabolic status by fasting blood test, and the organ damage variables by submaximal exercise treadmill test (ETT) and ultrasonic cardiogram (UCG) both on our inpatient and four-to-five weeks of outpatient part of CRP after ACS. We mainly used two-tailed Pearson's test and liner regression to evaluate the relationship of BMI/WC and organ damage. Our results confirmed that WC could be more accurate than BMI to evaluate the cardiac function through the changes of left ventricular structure on the CRP after ACS cases. It makes sense of early diagnosis, valid evaluation, and proper adjustment to ACS in CRP of the obesity individuals in the future. PMID:26247035

  1. Radiation-induced World Health Organization grade II meningiomas in young patients following prophylactic cranial irradiation for acute lymphoblastic leukemia in childhood. Three case reports.

    PubMed

    Oda, Keiko; Sato, Taku; Watanabe, Tadashi; Ichikawa, Masahiro; Ito, Eiji; Matsumoto, Yuka; Ando, Hitoshi; Sakuma, Jun; Kikuta, Atsushi; Hojo, Hiroshi; Saito, Kiyoshi

    2012-01-01

    Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia (ALL), but have resulted in an increased risk of late central nervous system tumors, most commonly meningioma, particularly in patients who have received cranial irradiation. We treated 3 young patients with World Health Organization grade II meningiomas who had previously received cranial irradiation for the treatment of childhood ALL: a cerebellopontine angle tumor in a 19-year-old woman, a petroclival tumor in a 28-year-old man, and a frontal parasagittal tumor in a 19-year-old woman. These cases were difficult to treat due to the aggressive and invasive biology of the tumors. Therefore, we recommend systematic cranial imaging and long follow-up periods for leukemia survivors to detect brain tumors before progression.

  2. Metabolic alterations in children with environmental enteric dysfunction.

    PubMed

    Semba, Richard D; Shardell, Michelle; Trehan, Indi; Moaddel, Ruin; Maleta, Kenneth M; Ordiz, M Isabel; Kraemer, Klaus; Khadeer, Mohammed; Ferrucci, Luigi; Manary, Mark J

    2016-06-13

    Environmental enteric dysfunction, an asymptomatic condition characterized by inflammation of the small bowel mucosa, villous atrophy, malabsorption, and increased intestinal permeability, is a major contributor to childhood stunting in low-income countries. Here we report the relationship of increased intestinal permeability with serum metabolites in 315 children without acute malnutrition, aged 12-59 months, in rural Malawi. Increased gut permeability was associated with significant differences in circulating metabolites that included lower serum phosphatidylcholines, sphingomyelins, tryptophan, ornithine, and citrulline, and elevated serum glutamate, taurine, and serotonin. Our findings suggest that environmental enteric dysfunction is characterized by alterations in important metabolites involved in growth and differentiation and gut function and integrity.

  3. Metabolic alterations in children with environmental enteric dysfunction

    PubMed Central

    Semba, Richard D.; Shardell, Michelle; Trehan, Indi; Moaddel, Ruin; Maleta, Kenneth M.; Ordiz, M. Isabel; Kraemer, Klaus; Khadeer, Mohammed; Ferrucci, Luigi; Manary, Mark J.

    2016-01-01

    Environmental enteric dysfunction, an asymptomatic condition characterized by inflammation of the small bowel mucosa, villous atrophy, malabsorption, and increased intestinal permeability, is a major contributor to childhood stunting in low-income countries. Here we report the relationship of increased intestinal permeability with serum metabolites in 315 children without acute malnutrition, aged 12–59 months, in rural Malawi. Increased gut permeability was associated with significant differences in circulating metabolites that included lower serum phosphatidylcholines, sphingomyelins, tryptophan, ornithine, and citrulline, and elevated serum glutamate, taurine, and serotonin. Our findings suggest that environmental enteric dysfunction is characterized by alterations in important metabolites involved in growth and differentiation and gut function and integrity. PMID:27294788

  4. Acute renal failure.

    PubMed

    Bellomo, Rinaldo

    2011-10-01

    Acute renal failure (now acute kidney injury) is a common complication of critical illness affecting between 30 and 60% of critically ill patients. The development of a consensus definition (RIFLE--risk, injury, failure, loss, end-stage system) has allowed standardization of reporting and epidemiological work. Multicenter multinational epidemiological studies indicate that sepsis is now the most common cause of acute renal failure in the intensive care unit (ICU) followed by cardiac surgery-associated acute kidney injury. Unfortunately, our understanding of the pathogenesis of acute renal failure in these settings remains limited. Because of such limited understanding, no reproducibly effective therapies have been developed. In addition the diagnosis of acute renal failure still rests upon the detection of changes in serum creatinine, which only occur if more than 50% of glomerular filtration is lost and are often delayed by more than 24 hours. Such diagnostic delays make the implementation of early therapy nearly impossible. In response to these difficulties, there has been a concerted effort to use proteomics to identify novel early biomarkers of acute renal failure. The identification and study of neutrophil gelatinase- associated lipocalin has been an important step in this field. Another area of active interest and investigation relates to the role of intravenous fluid resuscitation and fluid balance. Data from large observational studies and randomized, controlled trials consistently indicate that a positive fluid balance in patients with acute renal failure represents a major independent risk factor for mortality and provides no protection of renal function. The pendulum is clearly swinging away from a fluid-liberal approach to a fluid-conservative approach in these patients. Finally, there is a growing appreciation that acute renal failure may identify patients who are at increased risk of subsequent chronic renal dysfunction and mortality, opening the way

  5. Acute-on-chronic liver failure

    PubMed Central

    Asrani, Sumeet K; Simonetto, Douglas A; Kamath, Patrick S

    2015-01-01

    Over the last two decades, the concept of acute-on-chronic liver failure (ACLF) has been proposed as an alternate path in the natural history of decompensated cirrhosis. ACLF is thus characterized by the presence of a precipitating event (identified or unidentified) in subjects with underlying chronic liver disease leading to rapid progression of liver injury and ending in multi-organ dysfunction characterized by high short term mortality. Multiple organ failure and increased risk for mortality are key to diagnosis of ACLF. The prevalence of ACLF ranges from 24–40% in hospitalized patients. The pathophysiological basis of ACLF can be explained using a 4 part model of predisposing event, injury due to precipitating event, response to injury and organ failure. Though several mathematical scores have been proposed for identifying outcomes with ACLF, it is yet unclear whether these organ failure scores are truly prognostic or are only reflective of the dying process. Treatment paradigms continue to evolve but consist of early recognition, supportive intensive care, and consideration of liver transplantation prior to onset of irreversible multiple organ failure. PMID:26188138

  6. Visceral leishmaniasis in a kidney transplant recipient: parasitic interstitial nephritis, a cause of renal dysfunction.

    PubMed

    Dettwiler, S; McKee, T; Hadaya, K; Chappuis, F; van Delden, C; Moll, S

    2010-06-01

    Visceral leishmaniasis (VL) due to Leishmania infantum is an endemic parasitic infection in the Mediterranean area. It most commonly affects immunosuppressed individuals, especially HIV patients and less frequently organ transplant recipients. Renal involvement seems to be frequent and is mostly associated with tubulointerstitial nephritis, as described in autopsy reports. In the 61 cases of renal transplant recipients with VL reported in the literature, renal dysfunction was noted at clinical presentation and was more frequently observed as a complication of antiparasitic therapy. However, no pathological analysis of the allograft lesions was reported. We present the case of a Swiss renal transplant recipient who developed VL after vacations in Spain and Tunisia, complicated by acute parasitic nephritis in the renal allograft 3 months after a well-conducted treatment of liposomal amphotericin B.

  7. Diaphragm Dysfunction in Mechanically Ventilated Patients.

    PubMed

    Dot, Irene; Pérez-Teran, Purificación; Samper, Manuel-Andrés; Masclans, Joan-Ramon

    2017-03-01

    Muscle involvement is found in most critical patients admitted to the intensive care unit (ICU). Diaphragmatic muscle alteration, initially included in this category, has been differentiated in recent years, and a specific type of muscular dysfunction has been shown to occur in patients undergoing mechanical ventilation. We found this muscle dysfunction to appear in this subgroup of patients shortly after the start of mechanical ventilation, observing it to be mainly associated with certain control modes, and also with sepsis and/or multi-organ failure. Although the specific etiology of process is unknown, the muscle presents oxidative stress and mitochondrial changes. These cause changes in protein turnover, resulting in atrophy and impaired contractility, and leading to impaired functionality. The term 'ventilator-induced diaphragm dysfunction' was first coined by Vassilakopoulos et al. in 2004, and this phenomenon, along with injury cause by over-distention of the lung and barotrauma, represents a challenge in the daily life of ventilated patients. Diaphragmatic dysfunction affects prognosis by delaying extubation, prolonging hospital stay, and impairing the quality of life of these patients in the years following hospital discharge. Ultrasound, a non-invasive technique that is readily available in most ICUs, could be used to diagnose this condition promptly, thus preventing delays in starting rehabilitation and positively influencing prognosis in these patients.

  8. Thrombolysis in Chinese Ischemic Stroke Patients with Renal Dysfunction

    PubMed Central

    Lo, Wai Ting; Cheung, Chi Yuen; Li, Chung Ki; Chau, Ka Foon; Fong, Wing Chi

    2015-01-01

    Background Current data concerning the relationship between renal function and clinical outcome among stroke patients treated with intravenous thrombolytic therapy are conflicting. Our aim is to analyze whether the clinical outcome of Chinese ischemic stroke patients treated with thrombolytic therapy is affected by the presence of renal dysfunction. Methods Chinese patients who received intravenous thrombolytic therapy for acute ischemic stroke were recruited. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2. The primary outcome was independent function (modified Rankin Scale, mRS, 0-2) at 3 months, while secondary outcomes included early improvement of the National Institute of Health Stroke Scale (NIHSS) score of ≥4 points at 24 h, symptomatic intracerebral hemorrhage (ICH) within 36 h of treatment and 30-day mortality. Results A total of 199 patients were recruited, of whom 51.3% had renal dysfunction. There were no significant differences in functional independence at 3 months, NIHSS improvement at 24 h post-thrombolysis and 30-day mortality between patients with or without renal dysfunction. Multivariate analysis showed that eGFR as a continuous variable was not an independent risk factor for symptomatic ICH. Conclusion Chinese ischemic stroke patients with renal dysfunction who received thrombolytic therapy had clinical outcomes similar to those without renal dysfunction. PMID:26019713

  9. Arginase inhibitor in the pharmacological correction of endothelial dysfunction.

    PubMed

    Pokrovskiy, Mihail V; Korokin, Mihail V; Tsepeleva, Svetlana A; Pokrovskaya, Tatyana G; Gureev, Vladimir V; Konovalova, Elena A; Gudyrev, Oleg S; Kochkarov, Vladimir I; Korokina, Liliya V; Dudina, Eleonora N; Babko, Anna V; Terehova, Elena G

    2011-01-01

    THIS PAPER IS ABOUT A WAY OF CORRECTION OF ENDOTHELIAL DYSFUNCTION WITH THE INHIBITOR OF ARGINASE: L-norvaline. There is an imbalance between vasoconstriction and vasodilatation factors of endothelium on the basis of endothelial dysfunction. Among vasodilatation agents, nitrogen oxide plays the basic role. Amino acid L-arginine serves as a source of molecules of nitrogen oxide in an organism. Because of the high activity of arginase enzyme which catalyzes the hydrolysis of L-arginine into ornithine and urea, the bioavailability of nitrogen oxide decreases. The inhibitors of arginase suppress the activity of the given enzyme, raising and production of nitrogen oxide, preventing the development of endothelial dysfunction.

  10. Arginase Inhibitor in the Pharmacological Correction of Endothelial Dysfunction

    PubMed Central

    Pokrovskiy, Mihail V.; Korokin, Mihail V.; Tsepeleva, Svetlana A.; Pokrovskaya, Tatyana G.; Gureev, Vladimir V.; Konovalova, Elena A.; Gudyrev, Oleg S.; Kochkarov, Vladimir I.; Korokina, Liliya V.; Dudina, Eleonora N.; Babko, Anna V.; Terehova, Elena G.

    2011-01-01

    This paper is about a way of correction of endothelial dysfunction with the inhibitor of arginase: L-norvaline. There is an imbalance between vasoconstriction and vasodilatation factors of endothelium on the basis of endothelial dysfunction. Among vasodilatation agents, nitrogen oxide plays the basic role. Amino acid L-arginine serves as a source of molecules of nitrogen oxide in an organism. Because of the high activity of arginase enzyme which catalyzes the hydrolysis of L-arginine into ornithine and urea, the bioavailability of nitrogen oxide decreases. The inhibitors of arginase suppress the activity of the given enzyme, raising and production of nitrogen oxide, preventing the development of endothelial dysfunction. PMID:21747978

  11. Management of ejaculatory dysfunction.

    PubMed

    McMahon, C G

    2014-02-01

    Ejaculatory dysfunction is a common complaint and is often associated with a reduced quality of life for sufferer and partner. The spectrum of ejaculatory dysfunction extends from premature ejaculation (PE) to delayed ejaculation (DE) and anejaculation. Over the past 20-30 years, the PE treatment paradigm, previously limited to behavioural psychotherapy, has expanded to include drug treatment. Multiple well-controlled, evidence-based studies have demonstrated the efficacy and safety of selective serotonin re-uptake inhibitors in delaying ejaculation, confirming their role as first-line agents for the treatment of lifelong and acquired PE. More recently, there has been increased attention to the psychosocial consequences of PE, its epidemiology, its aetiology and its pathophysiology by both clinicians and the pharmaceutical industry. DE and anejaculation are probably the least common, least studied and least understood of the male sexual dysfunctions. However, their impact is significant as they may result in a lack of sexual fulfilment for both the man and his partner, an effect further compounded when procreation is among the couple's goals of sexual intercourse. The causes of DE, anejaculation and anorgasmia are manifold. Numerous psychotherapeutic treatments are described for the management of delayed or anejaculation. Although some appear to be effective, none has been properly evaluated in large-scale samples. Treatment of DE or anejaculation with pharmacotherapy has met with limited success. No drugs have been approved by regulatory agencies for this purpose, and most drugs that have been identified for potential use have limited efficacy, impart significant side-effects or are yet considered experimental in nature.

  12. [Thyroid dysfunctions and pregnancy].

    PubMed

    Caron, Philippe

    2011-12-01

    Advances in understanding the physiology of the thyroid function in normal pregnancy have highlighted the importance of the consequences of abnormal thyroid function on mother and fetal outcomes. Thyroid diseases are common in young women of childbearing age while management of thyroid diseases is relatively straightforward. For each thyroid dysfunction (hypothyroxinemia, hypothyroidism, hyperthyroidism, postpartum thyroiditis), the issues with the obstetric complications of the mother and the fetus are considered. Indeed, early recognition of thyroid diseases during pregnancy and appropriate management has the potential to improve outcome for the mother and the fetus.

  13. Dysfunctional voiding in adults.

    PubMed

    Haifler, Miki; Stav, Kobi

    2013-05-01

    Dysfunctional voiding is characterized by an intermittent and/or fluctuating flow rate due to involuntary intermittent contractions of the periurethral striated or levator muscles during voiding in neurologically normal women (International Continence Society definition). Due to the variable etiology, the diagnosis and treatment of DV is problematic. Frequently, the diagnosis is done at a late stage mainly due to non-specific symptoms and lack of awareness. The objectives of treatment are to normalize micturition patterns and prevent complications such as renal failure and recurrent infections. Treatment should be started as early as possible and a multidisciplinary approach is beneficial.

  14. Posttraumatic olfactory dysfunction.

    PubMed

    Coelho, Daniel H; Costanzo, Richard M

    2016-04-01

    Impairment of smell may occur following injury to any portion of the olfactory tract, from nasal cavity to brain. A thorough understanding of the anatomy and pathophysiology combined with comprehensively obtained history, physical exam, olfactory testing, and neuroimaging may help to identify the mechanism of dysfunction and suggest possible treatments. Although most olfactory deficits are neuronal mediated and therefore currently unable to be corrected, promising technology may provide novel treatment options for those most affected. Until that day, patient counseling with compensatory strategies and reassurance is essential for the maintenance of safety and QoL in this unique and challenging patient population.

  15. Depression and erectile dysfunction.

    PubMed

    Makhlouf, Antoine; Kparker, Ashay; Niederberger, Craig S

    2007-11-01

    Depression and erectile dysfunction (ED) clearly are associated. Although urologists and psychiatrists have long recognized that antidepressant medications affect erectile function negatively, the interplay between the two conditions remains underappreciated. Psychiatrists may be reluctant to question a patient in detail about ED, and urologists seldom perform a formal assessment of the presence of depression in patients who have ED. This article gives a quick overview of the relationship between these two conditions and provides the clinician with the knowledge required to effectively manage ED with comorbid depression.

  16. [Indices of tissue necrosis markers in acute pyo-destructive diseases of organs of the abdominal cavity].

    PubMed

    Ostrovskiĭ, V K; Makarov, S V; Rodionov, P N; Kochetkov, L N

    2011-01-01

    Investigation of indices of lactate dehydrogenase (LDG) and creatine phosphokinase (CPK) in a group of patients with extensive necrotic alterations in organs of the abdominal cavity and in a group of patients without extensive necroses has shown that in the first group there were higher levels of LDG and CPK. It shows that the LDG and CPK indices may be used as markers of tissue necrosis of the abdominal organs. In addition, in patients who died against the background of growing polyorganic insufficiency the LDG and CPK level by the end of treatment was statistically reliably higher than on admission of the same patients that may be an indicator of growing phenomena of dystrophy and micronecroses in vitals, so the indices of LDG and CPK may show the degree of severity of polyorganic insufficiency and determine its prognosis.

  17. Revenue, relationships and routines: the social organization of acute myocardial infarction patient transfers in the United States.

    PubMed

    Veinot, Tiffany C; Bosk, Emily A; Unnikrishnan, K P; Iwashyna, Theodore J

    2012-11-01

    Heart attack, or acute myocardial infarction (AMI), is a leading cause of death in the United States (U.S.). The most effective therapy for AMI is rapid revascularization: the mechanical opening of the clogged artery in the heart. Forty-four percent of patients with AMI who are admitted to a non-revascularization hospital in the U.S. are transferred to a hospital with that capacity. Yet, we know little about the process by which community hospitals complete these transfers, and why publicly available hospital quality data plays a small role in community hospitals' choice of transfer destinations. Therefore, we investigated how community hospital staff implement patient transfers and select destinations. We conducted a mixed methods study involving: interviews with staff at three community hospitals (n = 25) in a Midwestern state and analysis of U.S. national Medicare records for 1996-2006. Community hospitals in the U.S., including our field sites, typically had longstanding relationships with one key receiving hospital. Community hospitals addressed the need for rapid AMI patient transfers by routinizing the collective, interhospital work process. Routinization reduced staff uncertainty, coordinated their efforts and conserved their cognitive resources for patient care. While destination selection was nominally a physician role, the decision was routinized, such that staff immediately contacted a "usual" transfer destination upon AMI diagnosis. Transfer destination selection was primarily driven at an institutional level by organizational concerns and bed supply, rather than physician choice or patient preference. Transfer routinization emerged as a form of social order that invoked tradeoffs between process speed and efficiency and patient-centered, quality-driven decision making. We consider the implications of routinization and institutional imperatives for health policy, quality improvement and health informatics interventions.

  18. Managing female sexual dysfunction.

    PubMed

    Buster, John E

    2013-10-01

    Female sexual dysfunctions (FSDs) range from short-term aggravations to major emotional disturbances adversely affecting family and workplace. This review highlights diagnosis and management of the four most widely diagnosed FSDs. It initially focuses on hypoactive sexual desire disorder (HSDD) as a driving force at the heart of all other FSDs; nothing happens without sexual desire. Successful resolution of HSDD frequently facilitates resolution of other disorders. Central to understanding HSDD is the impact of aging female sexual endocrinology and its effect on both prevalence and expression patterns of FSD. Advances in this field have enabled introduction of some the most effective treatments yet described for HSDD. Sexual arousal disorder, though commonly affected by the same factors as HSDD, is heavily associated with psychotropic drugs and mood elevators. Orgasmic disorder is frequently the downstream result of other sexual dysfunctions, particularly HSDD, or the result of a major psychosexual trauma. Successful management of the underlying disorder often resolves orgasmic disorder. Sexual pain disorder is frequently the result of a gynecologic disorder, such as endometriosis, that can be substantially managed through successful treatment of that disorder. This article ends with the article's most important note: how to initiate the conversation.

  19. Animal models of erectile dysfunction.

    PubMed

    Kapoor, Mandeep Singh; Khan, Samsroz Ahmad; Gupta, Sanjay Kumar; Choudhary, Rajesh; Bodakhe, Surendra H

    2015-01-01

    Erectile dysfunction (ED) is a prevalent male sexual dysfunction with profound adverse effects on the physical and the psychosocial health of men and, subsequently, on their partners. The expanded use of various types of rodent models has produced some advances in the study of ED, and neurophysiological studies using various animal models have provided important insights into human sexual dysfunction. At present, animal models play a key role in exploring and screening novel drugs designed to treat ED.

  20. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  1. Autonomic dysfunction in multiple sclerosis.

    PubMed

    Racosta, Juan Manuel; Kimpinski, Kurt; Morrow, Sarah Anne; Kremenchutzky, Marcelo

    2015-12-01

    Autonomic dysfunction is a prevalent and significant cause of disability among patients with multiple sclerosis. Autonomic dysfunction in multiple sclerosis is usually explained by lesions within central nervous system regions responsible for autonomic regulation, but novel evidence suggests that other factors may be involved as well. Additionally, the interactions between the autonomic nervous system and the immune system have generated increased interest about the role of autonomic dysfunction in the pathogenesis of multiple sclerosis. In this paper we analyze systematically the most relevant signs and symptoms of autonomic dysfunction in MS, considering separately their potential causes and implications.

  2. Identifying and Extinguishing Dysfunctional and Deadly Organizational Practices

    ERIC Educational Resources Information Center

    Mawhinney, Thomas C.

    2009-01-01

    It is possible to define an organization's culture in terms of its dominant behavioral practices and their molar consequences, from the shop floor to the executive suite (Redmon & Mason, 2001). Dysfunctional and potentially deadly practices (for the organization as a whole) can be "latent." They often go undetected until their…

  3. Aged garlic extract improves homocysteine-induced endothelial dysfunction in macro- and microcirculation.

    PubMed

    Weiss, Norbert; Ide, Nagatoshi; Abahji, Thomas; Nill, Lars; Keller, Christiane; Hoffmann, Ulrich

    2006-03-01

    Endothelial dysfunction caused by increases in vascular oxidant stress that decrease bioavailable nitric oxide (NO) plays a critical role in the vascular pathobiology of hyperhomocysteinemia. Boosting cellular glutathione levels or increasing the activity of cellular glutathione peroxidase can compensate for homocysteine's effects on endothelial function. Aged garlic extract (AGE) contains water- and oil-soluble sulfur compounds that modify the intracellular thiol and redox state, minimize intracellular oxidant stress, and stimulate NO generation in endothelial cells and animals. We performed a placebo-controlled, blinded, crossover trial to examine whether AGE reduces macro- and microvascular endothelial dysfunction during acute hyperhomocysteinemia induced by an oral methionine challenge in healthy subjects. Acute hyperhomocysteinemia leads to a significant decrease in flow-mediated vasodilation of the brachial artery as determined by vascular ultrasound, indicative of macrovascular endothelial dysfunction. In addition, acute hyperhomocysteinemia leads to a decrease in acetylcholine-stimulated skin perfusion as measured by laser-Doppler flowmetry. This indicates microvascular endothelial dysfunction, which is presumably a result of impairment of the endothelium-derived hyperpolarizing factor pathway. Pretreatment with AGE for 6 wk significantly diminished the adverse effects of acute hyperhomocysteinemia in both vascular territories. We conclude that AGE may at least partly prevent a decrease in bioavailable NO and endothelium-derived hyperpolarizing factor during acute hyperhomocysteinemia. This pilot study warrants further investigations on the effects of AGE on endothelial dysfunction in patients with other cardiovascular risk factors or established vascular disease and on the clinical outcome of patients with cardiovascular disease.

  4. Acute treatment with bis selenide, an organic compound containing the trace element selenium, prevents memory deficits induced by reserpine in rats.

    PubMed

    Bortolatto, Cristiani Folharini; Guerra Souza, Ana Cristina; Wilhelm, Ethel Antunes; Nogueira, Cristina Wayne

    2013-01-01

    Taking into account the promising pharmacological actions of (Z)-2,3-bis(4-chlorophenylselanyl) prop-2-en-1-ol) (bis selenide), an organic compound containing the trace element selenium, and the constant search for drugs that improve the cognitive performance, the objective of the present study was to investigate whether bis selenide treatment ameliorates memory deficits induced by reserpine in rats. For this aim, male adult rats received a single subcutaneous injection of reserpine (1 mg/kg), a biogenic amine-depleting agent used to induce memory deficit. After 24 h, bis selenide at doses of 25 and 50 mg/kg was administered to rats by intragastric route, and 1 h later, the animals were submitted to behavior tasks. The effects of acute administration of bis selenide on memory were evaluated by social recognition, step-down passive avoidance, and object recognition paradigms. Exploratory and locomotor activities of rats were determined using the open-field test. Analysis of data revealed that the social memory disruption caused by reserpine was reversed by bis selenide at both doses. In addition, bis selenide, at the highest dose, prevented the memory deficit resulting from reserpine administration to rats in step-down passive avoidance and object recognition tasks. No significant alterations in locomotor and exploratory behaviors were found in animals treated with reserpine and/or bis selenide. Results obtained from distinct memory behavioral paradigms revealed that an acute treatment with bis selenide attenuated memory deficits induced by reserpine in rats.

  5. Risk-standardized Acute Admission Rates Among Patients With Diabetes and Heart Failure as a Measure of Quality of Accountable Care Organizations: Rationale, Methods, and Early Results

    PubMed Central

    Spatz, Erica S.; Lipska, Kasia J.; Dai, Ying; Bao, Haikun; Lin, Zhenqiu; Parzynski, Craig S.; Altaf, Faseeha K.; Joyce, Erin K.; Montague, Julia A.; Ross, Joseph S.; Bernheim, Susannah M.; Krumholz, Harlan M.; Drye, Elizabeth E.

    2017-01-01

    Background Population-based measures of admissions among patients with chronic conditions are important quality indicators of Accountable Care Organizations (ACOs), yet there are challenges in developing measures that enable fair comparisons among providers. Methods Based on consensus standards for outcome measure development and with expert and stakeholder input on methods decisions, we developed and tested two models of risk-standardized acute admission rates (RSAARs) for patients with diabetes and heart failure using 2010–2012 Medicare claims data. Model performance was assessed with deviance R-squared; score reliability was tested with intraclass correlation coefficient. We estimated RSAARs for 114 Shared Savings Program ACOs in 2012 and we assigned ACOs to 3 performance categories: no different, worse than, and better than the national rate. Results The diabetes and heart failure cohorts included 6.5 and 2.6 million Medicare fee-for-service (FFS) beneficiaries aged ≥65 years, respectively. Risk-adjustment variables were age, comorbidities and condition-specific severity variables, but not socioeconomic status or other contextual factors. We selected hierarchical negative binomial models with the outcome of acute, unplanned hospital admissions per 100 person-years. For the diabetes and heart failure measures respectively, the models accounted for 22% and 12% of the deviance in outcomes and score reliability was 0.89 and 0.77. For the diabetes measure, 51 (44.7%) ACOs were no different, 45 (39.5%) were better, and 18 (15.8%) were worse than the national rate. The distribution of performance for the heart failure measure was: 61 (53.5%);,37 (32.5%) and 16 (14.0%), respectively. Conclusion Measures of RSAARs for patients with diabetes and heart failure meet criteria for scientific soundness and reveal important variation in quality across ACOs. PMID:26918404

  6. Maternal and Fetal Blood and Organ Toluene Levels in Rats Following Acute and Repeated Binge Inhalation Exposure

    PubMed Central

    Bowen, Scott E.; Hannigan, John H.; Irtenkauf, Susan

    2007-01-01

    Inhalation of organic solvents is a persistent form of drug abuse with particular concern being the abuse of inhalants by women of child-bearing age. While studies have begun assessing postnatal outcomes of offspring exposed prenatally to inhalants, relatively little is known about the distribution of toluene in blood and body tissues of pregnant, inhalant-abusing women, or in the fetuses. The present study assessed the tissue toluene levels attained following brief toluene exposures using a pre-clinical rat model of maternal inhalant abuse. Timed-pregnant Sprague-Dawley rats were exposed to toluene at 8,000 or 12,000 parts per million (ppm) for 15, 30 or 45 min/exposure. Exposures occurred twice each day from gestational day 8 (GD8) through GD20. Immediately following the second exposure on GD8, GD14 and GD20 blood was taken from the saphenous vein of the dams. Following saphenous vein blood collection on GD20, dams were sacrificed and trunk blood was collected along with maternal tissue specimens from cerebellum, heart, lung, kidney and liver. The placenta, amniotic fluid and fetal brain were also collected. Results demonstrated that maternal saphenous blood toluene levels increased as the inhaled concentration of toluene and duration of exposure increased. The maternal cerebellum, heart, kidney and liver appeared to be saturated after 30 min on GD20 such that toluene levels in those organs were equivalent across all ambient concentrations of inhaled toluene. Toluene levels also increased in fetal brain as the inhaled concentration of toluene increased and in placenta and amniotic fluid as the duration of exposure increased. Toluene levels in all tissues at GD20, except maternal lung and amniotic fluid, were higher than in maternal saphenous blood suggesting that toluene concentrated in those organs. Measurement of toluene levels in blood and other tissues following repeated toluene exposure demonstrated that toluene readily reaches a variety of potential sites

  7. [The expertise evaluation of organization of rendering of acute, emergency and urgent medical care in rural regions of Novosibirsk oblast'].

    PubMed

    Ivaninskiĭ, O I; Sharapov, I V; Sadovoĭ, M A

    2013-01-01

    The most problematic spheres in the resource support of emergency medical care to rural residents are the completeness of staff of physicians in rural medical surgeries, community hospitals and departments of emergency medical care in central district hospitals. The provision of feldsher obstetrics posts with sanitary motor transport and medical equipment is yet another problematic sphere. The main troubles during provision of emergency medical care at feldsher obstetrics posts are related to surgery treatment. The organization of emergency and urgent medical care suffers of many unresolved problems related to informational program support at feldsher obstetrics posts, polyclinics of central district hospitals.

  8. Recognition and management of respiratory dysfunction in children with tetraplegia.

    PubMed

    Porth, Susan C

    2004-01-01

    Children less than 15 years of age comprise approximately 3% to 5% of all new spinal injuries each year. Approximately one third of these children sustain injuries to the cervical spine. Respiratory complications of spinal cord injuries at the level of C5 and above may include diaphragm dysfunction, retained airway secretions, recurrent aspiration, nocturnal hypoventilation, and respiratory failure. Although most newly injured children with cervical injuries above the level of C5 will require mechanical ventilation acutely, many eventually will be able to be weaned from technology. Despite their ability to breathe without mechanical support, these children often develop ongoing issues associated with respiratory compromise, which interfere with daily activities and can negatively affect quality of life. Poor endurance, failure to thrive, recurrent pneumonia, and sleep-disordered breathing all may be indications of significant respiratory dysfunction. This article describes assessment tools and management strategies aimed at supporting optimal health and preventing recurrent complications associated with unrecognized or untreated respiratory dysfunction.

  9. Predictive Performance of the Simplified Acute Physiology Score (SAPS) II and the Initial Sequential Organ Failure Assessment (SOFA) Score in Acutely Ill Intensive Care Patients: Post-Hoc Analyses of the SUP-ICU Inception Cohort Study

    PubMed Central

    Møller, Morten Hylander; Krag, Mette; Perner, Anders; Hjortrup, Peter Buhl

    2016-01-01

    Purpose Severity scores including the Simplified Acute Physiology Score (SAPS) II and the Sequential Organ Failure Assessment (SOFA) score are used in intensive care units (ICUs) to assess disease severity, predict mortality and in research. We aimed to assess the predictive performance of SAPS II and the initial SOFA score for in-hospital and 90-day mortality in a contemporary international cohort. Methods This was a post-hoc study of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) inception cohort study, which included acutely ill adults from ICUs across 11 countries (n = 1034). We compared the discrimination of SAPS II and initial SOFA scores, compared the discrimination of SAPS II in our cohort with the original cohort, assessed the calibration of SAPS II customised to our cohort, and compared the discrimination for 90-day mortality vs. in-hospital mortality for both scores. Discrimination was evaluated using areas under the receiver operating characteristics curves (AUROC). Calibration was evaluated using Hosmer-Lemeshow’s goodness-of-fit Ĉ-statistic. Results AUROC for in-hospital mortality was 0.80 (95% confidence interval (CI) 0.77–0.83) for SAPS II and 0.73 (95% CI 0.69–0.76) for initial SOFA score (P<0.001 for the comparison). Calibration of the customised SAPS II for predicting in-hospital mortality was adequate (P = 0.60). Discrimination of SAPS II was reduced compared with the original SAPS II validation sample (AUROC 0.80 vs. 0.86; P = 0.001). AUROC for 90-day mortality was 0.79 (95% CI 0.76–0.82; P = 0.74 for comparison with in-hospital mortality) for SAPS II and 0.71 (95% CI 0.68–0.75; P = 0.66 for comparison with in-hospital mortality) for the initial SOFA score. Conclusions The predictive performance of SAPS II was similar for in-hospital and 90-day mortality and superior to that of the initial SOFA score, but SAPS II’s performance has decreased over time. Use of a contemporary severity score with improved predictive

  10. Specific aspects of erectile dysfunction in psychiatry.

    PubMed

    Farre, J M; Fora, F; Lasheras, M G

    2004-10-01

    The participation of the psychiatrist in the management of erectile dysfunction (ED) is focused on three types of patients based on the origin of the dysfunction: (1) patients with functional or psychogenic ED, (2) patients with mixed, organic psychogenic ED, and (3) patients with ED and active psychopathology. The second group is influenced by three psychological factors: perpetuating factors, aggravating factors, and accompanying factors. The main psychopathological disorders that interfere directly with the erectile mechanism are depressive disorders (18-35%), anxiety disorders (37%), obsessive-compulsive disorder, psychotic disorders (46-47%), and the antipsychotic medications used to treat these disorders. The diagnostic proposal includes psychological and sexologic evaluation and differential diagnosis. The therapeutic proposal includes the basic principles of sex therapy in the model of behavioral-cognitive therapy (eg, prohibition of intercourse, sensate focus, voluntary loss of erections, no expectations about response), pharmacological therapy (eg, sildenafil, intracavernous injection of vasoactive drugs), and a combination of both therapies.

  11. Andropause: endocrinology, erectile dysfunction, and prostate pathophysiology.

    PubMed

    Hafez, B; Hafez, E S E

    2004-01-01

    This review summarizes major biological aspects of andrology of andropause, deficiency in androgens/growth hormones, and molecular parameters; erectile dysfunction (ED), the use of malleable, mechanical, inflatable devices as well as the application of Viagra (Sildenafil), alprotadil (Caverject), Yohimbine, and other drugs not yet approved by FDA, such as Papaverine, phentolamine (Vasomax), and apormorphine (Uprima); osteopenia/osteoporosis: testosterone/osteoporesis; supplementation during andropause: administration of andiogens, possible risk factors of androgens, calcium supplement and muscle mass; prostate pathophysiology: consequences of prostatectomy, prostate cancer, benign prostatic hyperplasia (BPH), hormone-dependent cancers; bladder and urethral dysfunction: neurological parameter, urodynamics technology; models on aging in male animals: comparative physiology of prostate of laboratory animals/farm animals; future research: functional anatomy of male reproductive organs, pharmacokinetics of osteoporosis, endocrinology/neuroendocrinology/chromosome anomalies supplementation during andropause, experimental animal models and future multicenter multidisciplinary research.

  12. An Organic Khorasan Wheat-Based Replacement Diet Improves Risk Profile of Patients with Acute Coronary Syndrome: A Randomized Crossover Trial<