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Multi organ dysfunction

Piotr T Filipczak, Cynthia L Thomas, Wenshu Chen, Andrew Salzman, Jacob D McDonald, Yong Lin, Steven A Belinsky
Tuberous sclerosis complex (TSC) is a genetic multi-organ disorder characterized by the development of neoplastic lesions in kidney, lung, brain, heart and skin. It is caused by an inactivating mutation in tumor suppressor genes coding the TSC1/TSC2 complex, resulting in hyperactivation of mTOR- and Raf/MEK/MAPK-dependent signaling that stimulates tumor cell proliferation and metastasis. Despite its oncogenic effect, cells with TSC deficiency were more sensitive to oxidative stress and dependent on mitochondrial metabolism, providing a rationale for a new therapeutic approach...
October 18, 2016: Cancer Research
Ranjeet Kumar, Candan Ariöz, Yaozong Li, Niklas Bosaeus, Sandra Rocha, Pernilla Wittung-Stafshede
After cellular uptake, Copper (Cu) ions are transferred from the chaperone Atox1 to the Wilson disease protein (ATP7B) for incorporation into Cu-dependent enzymes in the secretory pathway. Human ATP7B is a large multi-domain membrane-spanning protein which, in contrast to homologues in other organisms, has six similar cytoplasmic metal-binding domains (MBDs). The reason for multiple MBDs is proposed to be indirect modulation of enzymatic activity and it is thus intriguing that point mutations in MBDs can promote Wilson disease...
October 15, 2016: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Samuel M Brown, Jeffrey Sorensen, Michael J Lanspa, Matthew T Rondina, Colin K Grissom, Sajid Shahul, V J Mathews
BACKGROUND: Septic shock is a common and often devastating syndrome marked by severe cardiovascular dysfunction commonly managed with vasopressors. Whether markers of heart rate complexity before vasopressor up-titration could be used to predict success of the up-titration is not known. METHODS: We studied patients with septic shock requiring vasopressor, newly admitted to the intensive care unit. We measured the complexity of heart rate variability (using the ratio of fractal exponents from detrended fluctuation analysis) in the 5 min before all vasopressor up-titrations in the first 24 h of an intensive care unit (ICU) admission...
October 10, 2016: BMC Infectious Diseases
Jan Biegus, Robert Zymliński, Mateusz Sokolski, Paweł Siwołowski, Piotr Gajewski, Sylwia Nawrocka-Millward, Elżbieta Poniewierka, Ewa A Jankowska, Waldemar Banasiak, Piotr Ponikowski
AIM: Multi-organ dysfunction often complicates the natural course of acute heart failure (AHF) and identifies patients with poor prognosis. The MELD score (Model of End-Stage Liver Dysfunction) combines data reflecting liver and kidney function, which makes it a potentially useful tool for the assessment of patients with AHF. To assess the prognostic utility of the MELD score in patients with AHF. METHODS AND RESULTS: The MELD score was calculated on admission and during hospital stay (days 2-3) using a formula that does not take into account the international normalized ratio (MELD XI)...
October 6, 2016: European Journal of Heart Failure
Meric Kocaturk, Oya Eralp-Inan, A Tvarijonaviciute, Mehmet Cansev, M Ozgur Ozyigit, J J Ceron, Zeki Yilmaz, M Mufit Kahraman
The aim of the present study was to investigate effects of intravenous (i.v.) choline treatment on serum matrix metalloproteinases (MMP), MMP tissue inhibitors (TIMP) and immunoglobulins (Igs), and to determine if there were relations between serum MMPs/TIMPs and C-reactive protein (CRP) (as a marker of the acute phase response), immunoglobulin G and M (IgG and IgM) (as a maker of the Ig responses) and markers of organ damage such as muscular damage (creatine phosphokinase, [CPK]), liver damage (alanine aminotransferase [ALT]) and renal dysfunction (blood urea nitrogen [BUN] and creatinine, [Cr]) in dogs with endotoxemia...
November 1, 2016: Veterinary Immunology and Immunopathology
Kiyoshi Takasuna, Keiichi Asakura, Seiichi Araki, Hiroyuki Ando, Katsuyuki Kazusa, Takashi Kitaguchi, Takeshi Kunimatsu, Shinobu Suzuki, Norimasa Miyamoto
Recent increasing evidence suggests that the currently-used platforms in vitro IKr and APD, and/or in vivo QT assays are not fully predictive for TdP, and do not address potential arrhythmia (VT and/or VF) induced by diverse mechanisms of action. In addition, other cardiac safety liabilities such as functional dysfunction of excitation-contraction coupling (contractility) and structural damage (morphological damage to cardiomyocytes) are also major causes of drug attrition, but current in vitro assays do not cover all these liabilities...
September 17, 2016: Journal of Pharmacological and Toxicological Methods
Akbar Ahmad, Csaba Szabo
Hydrogen sulfide (H2S) exerts beneficial as well as deleterious effects in various models of critical illness. Here we tested the effect of two different pharmacological interventions: (a) inhibition of H2S biosynthesis using the cystathionine-beta-synthase (CBS)/cystathionine-gamma-lyase (CSE) inhibitor aminooxyacetic acid (AOAA) and the mitochondrially targeted H2S donor [10-oxo-10-[4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy]decyl]triphenyl-phosphonium (AP39). A 30% body surface area burn injury was induced in anesthetized mice; animals were treated with vehicle, AOAA (10mg/kg i...
September 14, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
P Cuny, M Houot, S Ginisty, S Horowicz, F Plassart, H Mentec, P Eftekhari
INTRODUCTION: The aim of this paper is to underline the need for systematic monitoring of patients treated with anticholinergic antipsychotic drugs. We present the clinical history of a 34-year-old adult, treated with quetiapine in combination with other drugs with anticholinergic effects. CASE REPORT: A 34-year-old male adult had been suffering from bipolar disorder since 2001. He was treated with risperidone, but he was not compliant due to adverse effects, including decreased libido and erectile dysfunction...
September 13, 2016: L'Encéphale
Sriram Pothapregada, Banupriya Kamalakannan, Mahalaskhmy Thulasingham, Srinivasan Sampath
OBJECTIVE: To study the clinical profile and outcome of dengue fever in children at a tertiary care hospital in Puducherry. MATERIALS AND METHODS: All children (0-12 years of age) diagnosed and confirmed as dengue fever from August 2012 to January 2015 were reviewed retrospectively from hospital case records as per the revised World Health Organization guidelines for dengue fever. The diagnosis was confirmed by NS1 antigen-based ELISA test or dengue serology for IgM and IgG antibodies, and the data were analyzed using SPSS 16...
July 2016: Journal of Global Infectious Diseases
Michael Kwok, Andrew Maurice, Carl Lisec, Jason Brown
INTRODUCTION: Campylobacter is the leading cause of bacterial diarrhoeal illness worldwide. Toxic megacolon is a rare but potentially devastating complication. PRESENTATION OF CASE: A 55year old female with liver cirrhosis, alcoholism and hepatitis C, presented with severe colitis and stool specimen positive for Campylobacter. She developed septic shock, multi-organ dysfunction syndrome and toxic megacolon unresponsive to medical therapy, and underwent a subtotal colectomy with end ileostomy...
2016: International Journal of Surgery Case Reports
Juan Zhou, Ian Burkovskiy, Hyewon Yang, Joel Sardinha, Christian Lehmann
The endocannabinoid system (ECS) is involved in many physiological processes and has been suggested to play a critical role in the immune response and the central nervous system (CNS). Therefore, ECS modulation has potential therapeutic effects on immune dysfunctional disorders, such as sepsis and CNS injury-induced immunodeficiency syndrome (CIDS). In sepsis, excessive release of pro- and anti-inflammatory mediators results in multi-organ dysfunction, failure, and death. In CIDS, an acute CNS injury dysregulates a normally well-balanced interplay between CNS and the immune system, leading to increased patients' susceptibility to infections...
2016: Frontiers in Pharmacology
Erik Hefti, Jonathan Bard, Javier G Blanco
Individuals with Down syndrome (DS, trisomy 21) exhibit a pro-oxidative cellular environment as well as mitochondrial dysfunction. Increased oxidative stress may damage the mitochondrial DNA (mtDNA). The coexistence of mtDNA variants in a cell or tissue (i.e., heteroplasmy) may contribute to mitochondrial dysfunction. Given the evidence on mitochondrial dysfunction and the relatively high incidence of multiorganic disorders associated with DS, we hypothesized that cardiac tissue from subjects with DS may exhibit higher frequencies of mtDNA variants in comparison to cardiac tissue from donors without DS...
September 4, 2016: Human Mutation
W Han, Y Han, J Chen, X Ma, F Chen, X J Wu, J Q Qi, H Y Qiu, A N Sun, D P Wu
OBJECTIVE: To analyze the clinical characteristics, treatment and prognosis of 16 allogeneic hematopoietic stem cell transplantation (allo- HSCT)- associated thrombotic microangiopathy (TA- TMA) patients. METHODS: The clinical data of 16 TA- TMA cases in 852 patients following allo- HSCT from Jan. 2013 to Jun. 2015 in the First Affiliated Hospital of Soochow University were retrospectively analyzed. RESULTS: Of all the 852 allo-HSCT recipients, 16 patients were diagnosed as TA-TMA and the 1-year cumulative incidence of TA-TMA was (2...
August 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Smruti B Vaishnav, Bhalendu Vaishnav, Kailas N Desai, Nitin S Raithatha, Neeta S Bose
BACKGROUND: There is a dearth of studies on the clinical profile and therapeutic aspects of critically ill obstetric patients from rural areas, especially those requiring tertiary care support and ventilator therapy. METHODS: We retrospectively analysed the aetiological, clinical, interventional and outcome-related factors of obstetric patients requiring mechanical ventilation in western India. We analysed factors that influence seeking of antenatal care, pregnancy and its complications, severity assessment score, indications and initiation of mechanical ventilation, multiorgan failure and their correlation with maternal mortality...
March 2016: National Medical Journal of India
Fabien Labombarda, Eric Saloux, Jacques Brouard, Emmanuel Bergot, Paul Milliez
Cystic fibrosis is a complex multi-systemic chronic disease characterized by progressive organ dysfunction with development of fibrosis, possibly affecting the heart. Over the last four decades pathological, experimental, and clinical evidence points towards the existence of a specific myocardial involvement in cystic fibrosis. Multi-modality cardiac imaging, especially recent echocardiographic techniques, evidenced diastolic and/or systolic ventricular dysfunction in cystic fibrosis leading to the concept of a cystic fibrosis-related cardiomyopathy...
September 2016: Respiratory Medicine
Rachel M Kaplan, Stanley A Swat, Benjamin D Singer
Human monocytic ehrlichiosis can manifest as a disease causing multi-organ failure. Rarely, it can cause secondary hemophagocytic lymphohistiocytosis (HLH). Early diagnosis and initiation of treatment for both ehrlichiosis and HLH is lifesaving. Therefore, clinical suspicion of HLH must remain high in the setting of an ehrlichiosis infection.
November 2016: Diagnostic Microbiology and Infectious Disease
Irene Dot, Purificación Pérez-Teran, Manuel-Andrés Samper, Joan-Ramon Masclans
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...
August 20, 2016: Archivos de Bronconeumología
Fabiola Mancini, Francesco Adamo, Roberta Creti, Monica Monaco, Giovanna Alfarone, Annalisa Pantosti, Alessandra Ciervo
We report the first human fatal case of streptococcal toxic shock syndrome (STSS) caused by Streptococcus suis serotype 2 carrying the tetracycline efflux tet (40) gene and the tetracycline ribosomal protection tet (O/W/32/O) gene. The patient was splenectomized. The case was characterized by multi-organ dysfunction and disseminated intravascular coagulopathy, in accordance with the clinical parameters of STSS. More investigations are needed to improve the epidemiology and the pathogenesis of S. suis in human infection...
August 20, 2016: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
David K Bailly, Ron W Reeder, Luke A Zabrocki, Anna M Hubbard, Jacob Wilkes, Susan L Bratton, Ravi R Thiagarajan
OBJECTIVE: Our objective was to develop and validate a prognostic score for predicting mortality at the time of extracorporeal membrane oxygenation initiation for children with respiratory failure. Preextracorporeal membrane oxygenation mortality prediction is important for determining center-specific risk-adjusted outcomes and counseling families. DESIGN: Multivariable logistic regression of a large international cohort of pediatric extracorporeal membrane oxygenation patients...
August 19, 2016: Critical Care Medicine
Shruti Chaturvedi, Djamila L Ghafuri, Jeffrey Glassberg, Adetola A Kassim, Mark Rodeghier, Michael R DeBaun
Current definitions of acute chest syndrome (ACS) in sickle cell anemia (SCA) do not account for rapid progression of respiratory compromise. In this two-center retrospective cohort study, we tested the hypothesis that in children and adults with ACS and respiratory failure (≤24 hours after onset of respiratory symptoms) have a distinct ACS phenotype associated with multiorgan failure when compared to those with ACS that have a more subacute and protracted course. We identified 173 individuals (97 children <20 years and 76 adults ≥20 years) with SCA and at least one episode of ACS...
August 20, 2016: American Journal of Hematology
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