ABSTRACT
Ethylene glycol is a toxic alcohol which may induce significant toxicity when ingested accidentally or intentionally. The main clinical complications of EG poisoning include central nervous system depression, cardiorespiratory instability and renal failure, which may be lethal if improperly treated. Although the demonstration of high plasma levels of ethylene glycol confirms the intoxication, such measurements are generally not obtained in the acute setting and can be misleading due to the rapid metabolism of EG. This implies the need for alternative, indirect, diagnostic methods, which reflect the metabolic fate of EG. These include an early and transient osmolar gap, followed by an anion gap metabolic acidosis and hyperoxaluria. Another frequent finding is a lactate gap between various methods of lactate measurements. An appropriate knowledge of these laboratory findings is essential for the diagnosis of EG poisoning, and for the initiation of antidote therapy (fomepizole) and hemodialysis in selected cases. These features are illustrated by the presentation of a prototypical case of EG poisoning, in which an incomplete diagnostic workup on hospital admission resulted in an unnecessary laparotomy and a significant delay in the management of the intoxication.
Subject(s)
Antidotes/administration & dosage , Ethylene Glycol/poisoning , Hyperoxaluria/etiology , Acidosis/etiology , Delayed Diagnosis , Female , Fomepizole/administration & dosage , Humans , Middle Aged , Poisoning/diagnosis , Poisoning/therapy , Renal Dialysis/methodsABSTRACT
BACKGROUND: Extracorporeal carbon dioxide removal (ECCO2R) is a promising technique for the management of acute respiratory failure, but with a limited level of evidence to support its use outside clinical trials and/or data collection initiatives. We report a collaborative initiative in a large metropolis. METHODS: To assess on a structural basis the rate of utilization as well as efficacy and safety parameters of 2 ECCO2R devices in 10 intensive care units (ICU) during a 2-year period. RESULTS: Seventy patients were recruited in 10 voluntary and specifically trained centers. The median utilization rate was 0.19 patient/month/center (min 0.04; max 1.20). ECCO2R was started under invasive mechanical ventilation (IMV) in 59 patients and non-invasive ventilation in 11 patients. The Hemolung Respiratory Assist System (Alung) was used in 53 patients and the iLA Activve iLA kit (Xenios Novalung) in 17 patients. Main indications were ultraprotective ventilation for ARDS patients (n = 24), shortening the duration of IMV in COPD patients (n = 21), preventing intubation in COPD patients (n = 9), and controlling hypercapnia and dynamic hyperinflation in mechanically ventilated patients with severe acute asthma (n = 6). A reduction in median V T was observed in ARDS patients from 5.9 to 4.1 ml/kg (p <0.001). A reduction in PaCO2 values was observed in AE-COPD patients from 67.5 to 51 mmHg (p< 0.001). Median duration of ECCO2R was 5 days (IQR 3-8). Reasons for ECCO2R discontinuation were improvement (n = 33), ECCO2R-related complications (n = 18), limitation of life-sustaining therapies or measures decision (n = 10), and death (n = 9). Main adverse events were hemolysis (n = 21), bleeding (n = 17), and lung membrane clotting (n = 11), with different profiles between the devices. Thirty-five deaths occurred during the ICU stay, 3 of which being ECCO2R-related. CONCLUSIONS: Based on a registry, we report a low rate of ECCO2R device utilization, mainly in severe COPD and ARDS patients. Physiological efficacy was confirmed in these two populations. We confirmed safety concerns such as hemolysis, bleeding, and thrombosis, with different profiles between the devices. Such results could help to design future studies aiming to enhance safety, to demonstrate a still-lacking strong clinical benefit of ECCO2R, and to guide the choice between different devices. TRIAL REGISTRATION: ClinicalTrials.gov: Identifier: NCT02965079 retrospectively registered https://clinicaltrials.gov/ct2/show/NCT02965079.
ABSTRACT
OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy wasdeveloped at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroupsand among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.(AU)
Subject(s)
Humans , Shock, Septic/drug therapy , Sepsis/drug therapy , Patient Care Planning , Respiration, Artificial , Vasoconstrictor Agents/therapeutic use , Calcitonin/therapeutic use , Nutrition Assessment , Chronic Disease/drug therapy , Renal Replacement Therapy , Fluid Therapy/methods , Anti-Bacterial Agents/administration & dosageABSTRACT
The occurrence of peritoneal carcinomatosis is a major cause of treatment failure in colorectal cancer and is considered incurable. However, new therapeutic approaches have been proposed, including cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Although HIPEC has been effective in selected patients, it is not known how HIPEC prolongs a patient's lifespan. Here, we have demonstrated that HIPEC-treated tumor cells induce the activation of tumor-specific T cells and lead to vaccination against tumor cells in mice. We have established that this effect results from the HIPEC-mediated exposure of heat shock protein (HSP) 90 at the plasma membrane. Inhibition or blocking of HSP90, but not HSP70, prevented the HIPEC-mediated antitumoral vaccination. Our work raises the possibility that the HIPEC procedure not only kills tumor cells but also induces an efficient anticancer immune response, therefore opening new opportunities for cancer treatment.
Subject(s)
Cancer Vaccines/pharmacology , HSP90 Heat-Shock Proteins/metabolism , Hyperthermia, Induced/methods , Peritoneal Neoplasms/immunology , Peritoneal Neoplasms/therapy , Animals , Cancer Vaccines/immunology , Cell Line, Tumor , Cell Membrane/metabolism , Coculture Techniques , Combined Modality Therapy , Dendritic Cells/immunology , HSP90 Heat-Shock Proteins/genetics , Humans , Mice, Inbred BALB C , Peritoneal Neoplasms/drug therapy , Xenograft Model Antitumor AssaysABSTRACT
Deregulated expression of glycolytic enzymes contributes not only to the increased energy demands of transformed cells but also has non-glycolytic roles in tumors. However, the contribution of these non-glycolytic functions in tumor progression remains poorly defined. Here, we show that elevated expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), but not of other glycolytic enzymes tested, increased aggressiveness and vascularization of non-Hodgkin's lymphoma. Elevated GAPDH expression was found to promote nuclear factor-κB (NF-κB) activation via binding to tumor necrosis factor receptor-associated factor-2 (TRAF2), enhancing the transcription and the activity of hypoxia-inducing factor-1α (HIF-1α). Consistent with this, inactive mutants of GAPDH failed to bind TRAF2, enhance HIF-1 activity or promote lymphomagenesis. Furthermore, elevated expression of gapdh mRNA in biopsies from diffuse large B-cell non-Hodgkin's lymphoma patients correlated with high levels of hif-1α, vegf-a, nfkbia mRNA and CD31 staining. Collectively, these data indicate that deregulated GAPDH expression promotes NF-κB-dependent induction of HIF-1α and has a key role in lymphoma vascularization and aggressiveness.
Subject(s)
Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Lymphoma, Non-Hodgkin/metabolism , NF-kappa B p50 Subunit/metabolism , Animals , Biopsy , Cell Line, Tumor , Enzyme Inhibitors/chemistry , HeLa Cells , Humans , Lymphoma/metabolism , Mice , Mice, Transgenic , Phenotype , Proto-Oncogene Proteins c-myc/metabolism , TNF Receptor-Associated Factor 2/metabolism , Vascular Endothelial Growth Factor A/metabolismABSTRACT
INTRODUCTION: Faecal peritonitis (FP) is a common cause of sepsis and admission to the intensive care unit (ICU). The Genetics of Sepsis and Septic Shock in Europe (GenOSept) project is investigating the influence of genetic variation on the host response and outcomes in a large cohort of patients with sepsis admitted to ICUs across Europe. Here we report an epidemiological survey of the subset of patients with FP. OBJECTIVES: To define the clinical characteristics, outcomes and risk factors for mortality in patients with FP admitted to ICUs across Europe. METHODS: Data was extracted from electronic case report forms. Phenotypic data was recorded using a detailed, quality-assured clinical database. The primary outcome measure was 6-month mortality. Patients were followed for 6 months. Kaplan-Meier analysis was used to determine mortality rates. Cox proportional hazards regression analysis was employed to identify independent risk factors for mortality. RESULTS: Data for 977 FP patients admitted to 102 centres across 16 countries between 29 September 2005 and 5 January 2011 was extracted. The median age was 69.2 years (IQR 58.3-77.1), with a male preponderance (54.3%). The most common causes of FP were perforated diverticular disease (32.1%) and surgical anastomotic breakdown (31.1%). The ICU mortality rate at 28 days was 19.1%, increasing to 31.6% at 6 months. The cause of FP, pre-existing co-morbidities and time from estimated onset of symptoms to surgery did not impact on survival. The strongest independent risk factors associated with an increased rate of death at 6 months included age, higher APACHE II score, acute renal and cardiovascular dysfunction within 1 week of admission to ICU, hypothermia, lower haematocrit and bradycardia on day 1 of ICU stay. CONCLUSIONS: In this large cohort of patients admitted to European ICUs with FP the 6 month mortality was 31.6%. The most consistent predictors of mortality across all time points were increased age, development of acute renal dysfunction during the first week of admission, lower haematocrit and hypothermia on day 1 of ICU admission.
Subject(s)
Feces , Peritonitis/mortality , Aged , Europe , Female , Health Surveys , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Multivariate Analysis , Peritonitis/epidemiology , Prognosis , Prospective Studies , Risk FactorsABSTRACT
Increased glucose catabolism and resistance to cell death are hallmarks of cancers, but the link between them remains elusive. Remarkably, under conditions where caspases are inhibited, the process of cell death is delayed but rarely blocked, leading to the occurrence of caspase-independent cell death (CICD). Escape from CICD is particularly relevant in the context of cancer as apoptosis inhibition only is often not sufficient to allow oncogenic transformation. While most glycolytic enzymes are overexpressed in tumors, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is of particular interest as it can allow cells to recover from CICD. Here, we show that GAPDH, but no other glycolytic enzymes tested, when overexpressed could bind to active Akt and limit its dephosphorylation. Active Akt prevents FoxO nuclear localization, which precludes Bcl-6 expression and leads to Bcl-xL overexpression. The GAPDH-dependent Bcl-xL overexpression is able to protect a subset of mitochondria from permeabilization that are required for cellular survival from CICD. Thus, our work suggests that GAPDH overexpression could induce Bcl-xL overexpression and protect cells from CICD-induced chemotherapy through preservation of intact mitochondria that may facilitate tumor survival and chemotherapeutic resistance.
Subject(s)
Apoptosis/physiology , Caspases/physiology , Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Up-Regulation/physiology , bcl-X Protein/metabolism , Cell Death/physiology , Cell Line, Tumor , Cell Survival/physiology , HEK293 Cells , HeLa Cells , Humans , Mitochondria/physiology , Phosphoglycerate Kinase/physiology , Phosphopyruvate Hydratase/physiology , Protein Binding/physiologyABSTRACT
Intensive care medical training, whether as a primary specialty or as secondary add-on training, should include key competences to ensure a uniform standard of care, and the number of intensive care physicians needs to increase to keep pace with the growing and anticipated need. The organisation of intensive care in multiple specialty or central units is heterogeneous and evolving, but appropriate early treatment and access to a trained intensivist should be assured at all times, and intensivists should play a pivotal role in ensuring communication and high-quality care across hospital departments. Structures now exist to support clinical research in intensive care medicine, which should become part of routine patient management. However, more translational research is urgently needed to identify areas that show clinical promise and to apply research principles to the real-life clinical setting. Likewise, electronic networks can be used to share expertise and support research. Individuals, physicians and policy makers need to allow for individual choices and priorities in the management of critically ill patients while remaining within the limits of economic reality. Professional scientific societies play a pivotal role in supporting the establishment of a defined minimum level of intensive health care and in ensuring standardised levels of training and patient care by promoting interaction between physicians and policy makers. The perception of intensive care medicine among the general public could be improved by concerted efforts to increase awareness of the services provided and of the successes achieved (AU)
La formación en medicina intensiva, ya sea como especialidad primaria o a partir de una troncalidad común para después convertirse en supra-especialidad, debería incluir competencias clave que garanticen un cuidado estándar y homogéneo del paciente crítico, así como proveer al sistema sanitario del número de especialistas en medicina intensiva (intensivistas) de forma ajustada y anticipada al ritmo de crecimiento de la necesidad asistencial. La organización de los cuidados intensivos desde la visión de las distintas especialidades o en unidades centralizadas y jerarquizadas, es heterogénea y está en constante evolución. No obstante el acceso y tratamiento precoz del enfermo crítico por parte de un intensivista, debería estar siempre garantizado, no únicamente en los servicios de medicina intensiva, sino en todos los departamentos de un hospital, actuando el intensivista como elemento central en la comunicación y coordinación entre los diferentes servicios y especialistas, a fin de lograr la más alta calidad y eficacia en la asistencia. La investigación clínica en medicina intensiva está sustentada por la excelencia de conocimiento de sus profesionales, pero son necesarias estructuras de apoyo: la integración de la investigación e innovación en la rutina diaria y un incremento de la investigación traslacional, a fin de identificar áreas que muestren elementos potenciales de avance en el aspecto clínico y la aplicación de los principios de la investigación básica y fisiológica en el entorno de la medicina intensiva. Las tecnologías de la comunicación y la información ofrecen un marco idóneo para compartir y poner en común el conocimiento y apoyar (..) (AU)
Subject(s)
Humans , Critical Care/trends , Intensive Care Units/trends , Specialization/trends , Health Services Research , Technological Development/policiesABSTRACT
Intensive care medical training, whether as a primary specialty or as secondary add-on training, should include key competences to ensure a uniform standard of care, and the number of intensive care physicians needs to increase to keep pace with the growing and anticipated need. The organisation of intensive care in multiple specialty or central units is heterogeneous and evolving, but appropriate early treatment and access to a trained intensivist should be assured at all times, and intensivists should play a pivotal role in ensuring communication and high-quality care across hospital departments. Structures now exist to support clinical research in intensive care medicine, which should become part of routine patient management. However, more translational research is urgently needed to identify areas that show clinical promise and to apply research principles to the real-life clinical setting. Likewise, electronic networks can be used to share expertise and support research. Individuals, physicians and policy makers need to allow for individual choices and priorities in the management of critically ill patients while remaining within the limits of economic reality. Professional scientific societies play a pivotal role in supporting the establishment of a defined minimum level of intensive health care and in ensuring standardised levels of training and patient care by promoting interaction between physicians and policy makers. The perception of intensive care medicine among the general public could be improved by concerted efforts to increase awareness of the services provided and of the successes achieved.
Subject(s)
Critical Care/trends , Medicine/trends , ForecastingABSTRACT
AIMS: Gut dysfunction is suspected to play a major role in the pathophysiology of post-resuscitation disease through an increase in intestinal permeability and endotoxin release. However this dysfunction often remains occult and is poorly investigated. The aim of this pilot study was to explore intestinal failure biomarkers in post-cardiac arrest patients and to correlate them with endotoxemia. METHODS: Following resuscitation after cardiac arrest, 21 patients were prospectively studied. Urinary intestinal fatty acid-binding protein (IFABP), which marks intestinal permeability, plasma citrulline, which reflects the functional enterocyte mass, and whole blood endotoxin were measured at admission, days 1-3 and 6. We explored the kinetics of release and the relationship between IFABP, citrulline and endotoxin values. RESULTS: IFABP was extremely high at admission and normalized at D3 (6668 pg/mL vs 39 pg/mL, p=0.01). Lowest median of citrulline (N=20-40 µmol/L) was attained at D2 (11 µmol/L at D2 vs 24 µmol/L at admission, p=0.01) and tended to normalize at D6 (21 µmol/L). During ICU stay, 86% of patients presented a detectable endotoxemia. Highest endotoxin level was positively correlated with highest IFABP level (R(2)=0.31, p=0.01) and was inversely correlated with lowest plasma citrulline levels (R(2)=0.55, p<0.001). Endotoxin levels increased between admission and D2 in patients with post-resuscitation shock, whereas it decreases in patients with no shock (median +0.33 EU vs -0.19 EU, p=0.03). Highest endotoxin level was positively correlated with D3 SOFA score (R(2)=0.45, p=0.004). CONCLUSION: Biomarkers of intestinal injury are altered after cardiac arrest and are associated with endotoxemia. This could worsen post-resuscitation shock and organ failure.
Subject(s)
Biomarkers/metabolism , Intestines/physiopathology , Out-of-Hospital Cardiac Arrest/metabolism , Out-of-Hospital Cardiac Arrest/therapy , Cardiopulmonary Resuscitation , Chromatography, High Pressure Liquid , Citrulline/blood , Endotoxemia/blood , Endotoxemia/physiopathology , Endotoxins/blood , Enzyme-Linked Immunosorbent Assay , Fatty Acid-Binding Proteins/urine , Female , Humans , Intestinal Mucosa/metabolism , Luminescence , Male , Middle Aged , Prospective Studies , Statistics, NonparametricABSTRACT
OBJECTIVES: To define a set of indicators that could be used to improve quality in intensive care medicine. METHODOLOGY: An European Society of Intensive Care Medicine Task Force on Quality and Safety identified all commonly used key quality indicators. This international Task Force consisted of 18 experts, all with a self-proclaimed interest in the area. Through a modified Delphi process seeking greater than 90% consensual agreement from this nominal group, the indicators were then refined through a series of iterative processes. RESULTS: A total of 111 indicators of quality were initially found, and these were consolidated into 102 separate items. After five discrete rounds of debate, these indicators were reduced to a subset of nine that all had greater than 90% agreement from the nominal group. These indicators can be used to describe the structures (3), processes (2) and outcomes (4) of intensive care. Across this international group, it was much more difficult to obtain consensual agreement on the indicators describing processes of care than on the structures and outcomes. CONCLUSION: This document contains nine indicators, all of which have a high level of consensual agreement from an international Task Force, which could be used to improve quality in routine intensive care practice.
Subject(s)
Critical Care/standards , Critical Illness , Patient Safety , Quality Improvement , Quality Indicators, Health Care , Advisory Committees , Delphi Technique , Europe , Humans , Prospective StudiesABSTRACT
PURPOSE: Septic shock induces a decrease in dendritic cells (DCs) that may contribute to sepsis-induced immunosuppression. We analyzed the time course of circulating DCs in patients with septic shock and its relation to susceptibility to intensive care unit (ICU)-acquired infections. METHODS: We enrolled adult patients with septic shock (n = 43), non-septic shock (n = 29), and with sepsis without organ dysfunction (n = 16). Healthy controls (n = 16) served as reference. Blood samples were drawn on the day of shock (day 1), then after 3 and 7 days. Myeloid (mDC) and plasmacytoid (pDC) DCs were counted by flow cytometry. Cell surface HLA-DR expression was analyzed in both DC subsets. RESULTS: At day 1, median mDC and pDC counts were dramatically lower in septic shock patients as compared to healthy controls (respectively, 835 mDCs and 178 pDCs/ml vs. 19,342 mDCs and 6,169 pDCs/ml; P < 0.0001) but also to non-septic shock and sepsis patients (P < 0.0001). HLA-DR expression was decreased in both mDCs and pDCS within the septic shock group as compared to healthy controls. DC depletion was sustained for at least 7 days in septic shock patients. Among them, 10/43 developed ICU-acquired infections after a median of 9 [7.5-11] days. At day 7, mDC counts increased in patients devoid of secondary infections, whereas they remained low in those who subsequently developed ICU-acquired infections. CONCLUSION: Septic shock is associated with profound and sustained depletion of circulating DCs. The persistence of low mDC counts is associated with the development of ICU-acquired infections, suggesting that DC depletion is a functional feature of sepsis-induced immunosuppression.
Subject(s)
Cross Infection , Dendritic Cells/immunology , Intensive Care Units , Shock, Septic/blood , Shock, Septic/physiopathology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Survival AnalysisABSTRACT
INTRODUCTION: Early use of corticosteroids in patients affected by pandemic (H1N1)v influenza A infection, although relatively common, remains controversial. METHODS: Prospective, observational, multicenter study from 23 June 2009 through 11 February 2010, reported in the European Society of Intensive Care Medicine (ESICM) H1N1 registry. RESULTS: Two hundred twenty patients admitted to an intensive care unit (ICU) with completed outcome data were analyzed. Invasive mechanical ventilation was used in 155 (70.5%). Sixty-seven (30.5%) of the patients died in ICU and 75 (34.1%) whilst in hospital. One hundred twenty-six (57.3%) patients received corticosteroid therapy on admission to ICU. Patients who received corticosteroids were significantly older and were more likely to have coexisting asthma, chronic obstructive pulmonary disease (COPD), and chronic steroid use. These patients receiving corticosteroids had increased likelihood of developing hospital-acquired pneumonia (HAP) [26.2% versus 13.8%, p < 0.05; odds ratio (OR) 2.2, confidence interval (CI) 1.1-4.5]. Patients who received corticosteroids had significantly higher ICU mortality than patients who did not (46.0% versus 18.1%, p < 0.01; OR 3.8, CI 2.1-7.2). Cox regression analysis adjusted for severity and potential confounding factors identified that early use of corticosteroids was not significantly associated with mortality [hazard ratio (HR) 1.3, 95% CI 0.7-2.4, p = 0.4] but was still associated with an increased rate of HAP (OR 2.2, 95% CI 1.0-4.8, p < 0.05). When only patients developing acute respiratory distress syndrome (ARDS) were analyzed, similar results were observed. CONCLUSIONS: Early use of corticosteroids in patients affected by pandemic (H1N1)v influenza A infection did not result in better outcomes and was associated with increased risk of superinfections.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Influenza A Virus, H1N1 Subtype/drug effects , Influenza, Human/drug therapy , Intensive Care Units , Pandemics , Severity of Illness Index , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Adult , Cross Infection/epidemiology , Europe/epidemiology , Female , Humans , Likelihood Functions , Male , Middle Aged , Pneumonia/epidemiology , Prospective Studies , Registries/statistics & numerical data , Survival AnalysisABSTRACT
We describe a rare case of multifocal necrotizing fasciitis (NF) complicating a single vaccine injection. Injection of hepatitis B vaccine of a 16-year-old immunocompetent woman developed into rapidly spreading multifocal NF of the right arm and the thighs, with septic shock. Treatment with antimicrobial therapy and surgical debridements allowed amputation to be avoided with a favourable outcome. The etiological agent was a methicillin-sensitive Staphylococcus aureus (MSSA) isolate harboring the Panton-Valentine leukocidin (PVL) and five enterotoxins. PVL has recently been reported in large series of methicillin-resistant SA cases and has been associated with necrotizing infections. Some strains of MSSA could harbor PVL and enterotoxins. PCR investigation is not frequent but could improve the understanding of the mechanisms of lesions. This case is in keeping with the increasing incidence of MSSA harboring PVL and enterotoxins with multifocal dissemination NF and emphasizes the necessary precautions for skin decontamination before vaccine injection.
Subject(s)
Bacterial Toxins/biosynthesis , Community-Acquired Infections/microbiology , Exotoxins/biosynthesis , Fasciitis, Necrotizing/microbiology , Leukocidins/biosynthesis , Staphylococcus aureus/isolation & purification , Adolescent , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Toxins/genetics , Community-Acquired Infections/drug therapy , Community-Acquired Infections/surgery , Exotoxins/genetics , Fasciitis, Necrotizing/drug therapy , Fasciitis, Necrotizing/surgery , Female , Humans , Leukocidins/genetics , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Staphylococcus aureus/drug effects , Staphylococcus aureus/metabolismABSTRACT
The fourth edition of the BIRADS mammography appeared in 2003 and is now associated with the first editions of the BIRADS ultrasound and MRI. BIRADS is a system of assistance to the drafting of the reports more and more used in the world and soon directly implemented on mammography and ultrasound units. The categories of evaluation of the BIRADS allow a clear synthesis of the descriptive data resulting from the use of the lexicon and invite the radiologist to a reasoned, objective and less intuitive step. They give an action to be taken and responsibility to the radiologist and the referring physicians in the assumption of the patients.
Subject(s)
Breast Neoplasms/diagnostic imaging , Radiology Information Systems , Ultrasonography/classification , Vocabulary, Controlled , Calcinosis/diagnostic imaging , Humans , Mammography/classificationABSTRACT
INTRODUCTION: Esophageal Doppler provides a continuous and non-invasive estimate of descending aortic blood flow (ABF) and corrected left ventricular ejection time (LVETc). Considering passive leg raising (PLR) as a reversible volume expansion (VE), we compared the relative abilities of PLR-induced ABF variations, LVETc and respiratory pulsed pressure variations (DeltaPP) to predict fluid responsiveness. METHODS: We studied 22 critically ill patients in acute circulatory failure in the supine position, during PLR, back to the supine position and after two consecutive VEs of 250 ml of saline. Responders were defined by an increase in ABF induced by 500 ml VE of more than 15%. RESULTS: Ten patients were responders and 12 were non-responders. In responders, the increase in ABF induced by PLR was similar to that induced by a 250 ml VE (16% versus 20%; p = 0.15). A PLR-induced increase in ABF of more than 8% predicted fluid responsiveness with a sensitivity of 90% and a specificity of 83%. Corresponding positive and negative predictive values (PPV and NPV, respectively) were 82% and 91%, respectively. A DeltaPP threshold value of 12% predicted fluid responsiveness with a sensitivity of 70% and a specificity of 92%. Corresponding PPV and NPV were 87% and 78%, respectively. A LVETc of 245 ms or less predicted fluid responsiveness with a sensitivity of 70%, and a specificity of 67%. Corresponding PPV and NPV were 60% and 66%, respectively. CONCLUSION: The PLR-induced increase in ABF and a DeltaPP of more than 12% offer similar predictive values in predicting fluid responsiveness. An isolated basal LVETc value is not a reliable criterion for predicting response to fluid loading.
Subject(s)
Aorta, Thoracic/physiology , Critical Illness/epidemiology , Critical Illness/therapy , Fluid Therapy , Leg/blood supply , Supine Position/physiology , Aged , Blood Flow Velocity/physiology , Female , Humans , Leg/physiology , Male , Middle Aged , Predictive Value of TestsABSTRACT
BI-RADS is a system of assistance to the drafting of the reports more and more used in the world and soon directly implemented on mammography and ultrasound units. The categories of evaluation of the BI-RADS allow a clear synthesis of the descriptive data resulting from the use of the lexicon and invite the radiologist to a reasoned, objective and less intuitive step. They give an action to be taken and responsibility to the radiologist and the referring physicians in the assumption of the patients. The 4th edition of the BI-RADS mammography appeared in 2003, and is now associated with the first editions of the BI-RADS ultrasound and MRI.
Subject(s)
Breast Diseases/diagnostic imaging , Databases, Bibliographic , Mammography , Breast Neoplasms/diagnostic imaging , Calcinosis/diagnostic imaging , England , Female , Fibroadenoma/diagnostic imaging , France , Humans , Language , SoftwareABSTRACT
In vascular smooth muscle cells, NO stimulates the synthesis of cGMP by soluble guanylate cyclase (sGC), a heterodimer composed of alpha(1) and beta(1) subunits. NO/cGMP signal transduction affects multiple cell functions that contribute to neointima formation after vascular injury. Balloon-induced vascular injury was found to decrease sGC subunit expression and enzyme activity in rat carotid arteries. The effect of restoring sGC enzyme activity on neointima formation was investigated using recombinant adenoviruses specifying sGC alpha(1) and beta(1) subunits (Adalpha1 and Adbeta1). Coinfection of cultured rat aortic smooth muscle cells with Adalpha1 and Adbeta1 increased NO-stimulated intracellular cGMP levels 60-fold and decreased DNA synthesis and migration by 16% and 48%, respectively. Immunoreactivity for alpha(1) and beta(1) subunits colocalized in carotid arteries infected with Adalpha1 and Adbeta1. Molsidomine-stimulated carotid tissue cGMP levels were greater after coinfection with Adalpha1 and Adbeta1 than after infection with a control virus, AdRR5 (0.53+/-0.09 pmol/mg protein, mean+/-SEM, versus 0.23+/-0.09, P<0.05). Mean intima/media ratio, 2 weeks after balloon injury and twice-daily administration of 5 mg/kg molsidomine, was less in rats coinfected with Adalpha1 and Adss1 than in rats infected with AdRR5 or in uninfected rats (0.36+/-0.11 versus 0. 81+/-0.13 and 0.75+/-0.25, respectively, P<0.05). Thus, Adalpha1 and Adbeta1 gene transfer to balloon-injured rat carotid arteries increases NO responsiveness and attenuates neointima formation via a direct antiproliferative and antimigratory effect on vascular smooth muscle cells.
Subject(s)
Carotid Artery Injuries/physiopathology , Guanylate Cyclase/metabolism , Nitric Oxide/physiology , Tunica Intima/physiopathology , Angioplasty, Balloon/adverse effects , Animals , Carotid Arteries/drug effects , Carotid Arteries/metabolism , Carotid Arteries/physiopathology , Carotid Artery Injuries/etiology , Carotid Artery Injuries/genetics , Cell Division/drug effects , Cell Movement/drug effects , Cells, Cultured , Cyclic GMP/metabolism , Gene Transfer Techniques , Guanylate Cyclase/genetics , Molsidomine/pharmacology , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Nitric Oxide Donors/pharmacology , Rats , Solubility , Tunica Intima/drug effectsABSTRACT
Partial liquid ventilation (PLV) improves oxygenation in several models of lung injury. However, PLV has only been compared with conventional gas ventilation (GV) with low PEEP. Both PLV and GV can markedly improve oxygenation when PEEP is set above the lower corner pressure (Plc) on the inspiratory pressure-volume (P-V) curve of the total respiratory system. We questioned if the use of PEEP set above the Plc during PLV and GV would result in similar gas exchange. Lung injury was induced in 12 sheep by saline lavage before randomization to PLV (n = 6) or GV (n = 6). Animals in the PLV group were filled with perflubron (22 ml/kg) until a meniscus at the teeth was observed. Both groups were then ventilated with pressure control (FI(O(2)), 1.0; rate, 20/min; I:E, 1:1) and PEEP (1 cm H(2)O above the Plc on the inspiratory P-V curve). Peak inspiratory pressure (PIP) was limited to 35 cm H(2)O. Animals were ventilated for 5 h and then killed for histologic examinations. All 12 animals survived the 5-h ventilation period. After increasing PEEP above Plc, Pa(O(2)) increased significantly (p < 0.01) in both the GV and the PLV groups, but it did not differ significantly between groups (p = 0.86) at any time during the experiment. Pa(CO(2)) and VD/VT in GV increased markedly throughout the experiment after increasing PEEP (p < 0.001), but there was no significant change in Pa(CO(2)) in PLV (p = 0.13). Mean arterial blood pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure, and central venous pressure, increased and SVR decreased in GV (p < 0.05). The extent and the severity of lung injury in the dependent regions was greater in the GV group (p < 0.05). Both PLV and GV improved oxygenation, but PLV resulted in better ventilation than GV while preserving lung structure when PEEP was set 1 cm H(2)O above the Plc and PIP limited to 35 cm H(2)O.
Subject(s)
Respiration, Artificial/methods , Animals , Carbon Dioxide/analysis , Gases , Hemodynamics/physiology , Lung/cytology , Partial Pressure , Positive-Pressure Respiration , Pulmonary Gas Exchange/physiology , Random Allocation , Respiratory Mechanics/physiology , SheepABSTRACT
The nuclear body is a multiprotein complex that may have a role in the regulation of gene transcription. This structure is disrupted in a variety of human disorders including acute promyelocytic leukemia and viral infections, suggesting that alterations in the nuclear body may have an important role in the pathogenesis of these diseases. In this study, we identified a cDNA encoding a leukocyte-specific nuclear body component designated Sp110. The N-terminal portion of Sp110 was homologous to two previously characterized components of the nuclear body (Sp100 and Sp140). The C-terminal region of Sp110 was homologous to the transcription intermediary factor 1 (TIF1) family of proteins. High levels of Sp110 mRNA were detected in human peripheral blood leukocytes and spleen but not in other tissues. The levels of Sp110 mRNA and protein in the human promyelocytic leukemia cell line NB4 increased following treatment with all-trans retinoic acid (ATRA), and Sp110 localized to PML-Sp100 nuclear bodies in ATRA-treated NB4 cells. Because of the structural similarities between Sp110 and TIF1 proteins, the effect of Sp110 on gene transcription was examined. An Sp110 DNA-binding domain fusion protein activated transcription of a reporter gene in transfected mammalian cells. In addition, Sp110 produced a marked increase in ATRA-mediated expression of a reporter gene containing a retinoic acid response element. Taken together, the results of this study demonstrate that Sp110 is a member of the Sp100/Sp140 family of nuclear body components and that Sp110 may function as a nuclear hormone receptor transcriptional coactivator. The predominant expression of Sp110 in leukocytes and the enhanced expression of Sp110 in NB4 cells treated with ATRA raise the possibility that Sp110 has a role in inducing differentiation of myeloid cells.