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https://www.readbyqxmd.com/read/28522374/population-pharmacokinetics-of-nnz-2566-in-healthy-subjects
#1
Sean P Oosterholt, Joseph Horrigan, Nancy Jones, Larry Glass, Oscar Della Pasqua
NNZ-2566 is a novel, small molecule being developed as a treatment for cognitive impairment in different CNS conditions, including Rett and Fragile-X syndrome, both of which are associated with moderate to severe neurodevelopmental disorder. In current study we characterise the population pharmacokinetics of NNZ-2566 after administration of single and repeated ascending doses to healthy subjects. A meta-analytical approach was used to analyse pharmacokinetic data from 3 different studies, in which a total of 61 healthy subjects (median age 23years, range 19 to 38) were treated with NNZ-2566...
May 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28451756/thymus-neuroendocrine-tumors-with-ctnnb1-gene-mutations-disarrayed-%C3%A3-catenin-expression-and-dual-intra-tumor-ki-67-labeling-index-compartmentalization-challenge-the-concept-of-secondary-high-grade-neuroendocrine-tumor-a-paradigm-shift
#2
Alessandra Fabbri, Mara Cossa, Angelica Sonzogni, Paolo Bidoli, Stefania Canova, Diego Cortinovis, Maria Ida Abbate, Fiorella Calabrese, Nazarena Nannini, Francesca Lunardi, Giulio Rossi, Stefano La Rosa, Carlo Capella, Elena Tamborini, Federica Perrone, Adele Busico, Iolanda Capone, Barbara Valeri, Ugo Pastorino, Adriana Albini, Giuseppe Pelosi
We herein report an uncommon association of intimately admixed atypical carcinoid (AC) and large cell neuroendocrine (NE) carcinoma (LCNEC) of the thymus, occurring in two 20- and 39-year-old Caucasian males. Both tumors were treated by maximal thymectomy. The younger patient presented with a synchronous lesion and died of disease after 9 months, while the other patient was associated with a recurrent ectopic adrenocorticotropic hormone Cushing's syndrome and is alive with disease at the 2-year follow-up. MEN1 syndrome was excluded in either case...
April 27, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28410500/cancer-is-a-propagandist
#3
Giamila Fantuzzi
Communication among cells (also known as cross-talk) plays a prominent role in the current knowledge of the pathophysiology of cancer and of cancer-associated conditions such as paraneoplastic syndromes and cachexia that are responsible for much of cancer's morbidity and mortality. Yet, biomedical scientists lack an explicit unifying frame that places this exchange of molecular information at the core of their understanding of cancer as a systemic disease. Propaganda is a type of information that aims at misleading, a form of communication intended primarily to serve the messenger...
April 11, 2017: Studies in History and Philosophy of Biological and Biomedical Sciences
https://www.readbyqxmd.com/read/28383502/the-role-of-hiv-infection-in-neurologic-injury
#4
REVIEW
Rossana Scutari, Claudia Alteri, Carlo Federico Perno, Valentina Svicher, Stefano Aquaro
The central nervous system (CNS) is a very challenging HIV-1 sanctuary, in which HIV-1 replication is established early on during acute infection and can persist despite potent antiretroviral treatments. HIV-1 infected macrophages play a pivotal role acting as vehicles for HIV-1 to spread into the brain, and can be the major contributor of an early compartmentalization. HIV-1 infection in CNS may lead to a broad spectrum of neurological syndromes, such as dementia, mild neurocognitive disorders, and asymptomatic impairment...
April 6, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28288182/modelling-optimal-allocation-of-resources-in-the-context-of-an-incurable-disease
#5
Betty Nannyonga, David J T Sumpter
Nodding syndrome has affected and led to the deaths of children between the ages of 5 and 15 in Northern Uganda since 2009. There is no reliable explanation of the disease, and currently the only treatment is through a nutritional programme of vitamins, combined with medication to prevent symptoms. In the absence of a proper medical treatment, we develop a dynamic compartmental model to plan the management of the syndrome and to curb its effects. We use incidence data from 2012 and 2013 from Pader, Lamwo and Kitgum regions of Uganda to parameterize the model...
2017: PloS One
https://www.readbyqxmd.com/read/28194389/elastic-suture-shoelace-technique-for-fasciotomy-closure-after-treatment-of-compartmental-syndrome-associated-to-tibial-fracture
#6
Paulo Sergio Martins Castelo Branco, Mauricio Cardoso Junior, Isaac Rotbande, José Antonio Fraga Ciraudo, Celso Ricardo Correa de Melo Silva, Paulo Cesar Dos Santos Leal
This article reports the use of elastic suture as an adjuvant in surgical wound closure caused by decompressive fasciotomy after compartment syndrome associated with a compound fracture of the tibia. Widely used in other medico-surgical specialties, this technique is unusual in orthopedics surgery, but the simplicity of the procedure and the successful outcome observed in this case allows for its consideration as indicated for situations similar to that presented in this study.
January 2017: Revista Brasileira de Ortopedia
https://www.readbyqxmd.com/read/28187791/primary-mediastinal-large-b-cell-lymphoma-in-a-woman-who-is-human-immunodeficiency-virus-positive-presenting-with-superior-vena-cava-syndrome-a-case-report
#7
Pedro Pallangyo, Paulina Nicholaus, Frederick Lyimo, Elikaanany Urio, Peter Kisenge, Mohamed Janabi
BACKGROUND: The risk of non-Hodgkin lymphoma is increased 200-fold in individuals seropositive for human immunodeficiency virus compared to those free from human immunodeficiency virus. Human immunodeficiency virus-associated non-Hodgkin lymphoma is known for its atypical presentation, aggressive ability, widespread involvement, poor response to chemotherapy, and high relapse potential which makes both the diagnosis and management a difficult undertaking especially in resource-poor settings...
February 11, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28048092/su-g-iep1-10-permeability-evaluation-of-interstitial-cystitis-by-dce-mri-of-the-bladder
#8
D Wu, J Vo, J North, R Towner, R Hurst
PURPOSE: Interstitial cystitis (IC) is a chronic and painful condition that can lead to bladder pain syndrome (BPS) in women. IC and BPS have been known to manifest after physiological changes after giving birth. In this project, we pioneered and advanced a new clinical utility using DCE-MRI to assess bladder permeability. At first IC/BPS perfusion methods were with ratio signal evaluation, we now incorporate pharmacokinetics techniques to allow for further assessment. METHODS: In this pilot study, female patients and volunteers (IC=4, Control=3) underwent imaging with a clinical GE 3T 750W MRI system...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28043728/acute-compartment-syndrome-caused-by-uncontrolled-hypothyroidism
#9
Anar Modi, Hari Amin, Matthew Salzman, Farah Morgan
Acute compartment syndrome is increased tissue pressure exceeding perfusion pressure in a closed compartment resulting in nerve and muscle ischemia. Common precipitating causes are crush injuries, burns, substance abuse, osseous or vascular limb trauma. This is a case of 42year old female with history of hypothyroidism who presented to emergency room with acute onset of severe pain and swelling in right lower extremity. Physical examination was concerning for acute compartment syndrome of right leg which was confirmed by demonstration of elevated compartmental pressures...
December 23, 2016: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28003319/hypothyroid-induced-acute-compartment-syndrome-in-all-extremities
#10
Matthew C Musielak, Jung Hee Chae
Acute compartment syndrome (ACS) is an uncommon complication of uncontrolled hypothyroidism. If unrecognized, this can lead to ischemia, necrosis and potential limb loss. A 49-year-old female presented with the sudden onset of bilateral lower and upper extremity swelling and pain. The lower extremity anterior compartments were painful and tense. The extensor surface of the upper extremities exhibited swelling and pain. Motor function was intact, however, limited due to pain. Bilateral lower extremity fasciotomies were performed...
December 20, 2016: Journal of Surgical Case Reports
https://www.readbyqxmd.com/read/27999729/a-non-operative-approach-to-the-management-of-chronic-exertional-compartment-syndrome-in-a-triathlete-a-case-report
#11
Cristiana Kahl Collins, Brad Gilden
BACKGROUND & PURPOSE: Chronic Exertional Compartment Syndrome (CECS) causes significant exercise related pain secondary to increased intra-compartmental pressure (ICP) in the lower extremities. CECS is most often treated with surgery with minimal information available on non-operative approaches to care. This case report presents a case of CECS successfully managed with physical therapy. STUDY DESIGN: Case report. CASE DESCRIPTION: A 34-year-old competitive triathlete experienced bilateral anterior and posterior lower leg pain measured with a numerical pain rating scale of 7/10 at two miles of running...
December 2016: International Journal of Sports Physical Therapy
https://www.readbyqxmd.com/read/27903048/resistance-exercise-induced-rhabdomyolysis-need-for-immediate-intervention-and-proper-counselling
#12
Maysaa A Khalil, Basem R Saab
BACKGROUND: Rhabdomyolysis results from damage to skeletal muscle. Improper resistance training may result in rhabdomyolysis, which can cause acute kidney injury, serious metabolic abnormalities, compartmental syndrome and even death. Proper counselling for athletes may prevent this condition. OBJECTIVE: We present two patients with unilateral swelling after resistance exercise. The workup revealed rhabdomyolysis. We highlight the importance of counselling to prevent rhabdomyolysis secondary to resistance exercise...
December 2016: Australian Family Physician
https://www.readbyqxmd.com/read/27881824/two-tissue-resident-progenitor-lineages-drive-distinct-phenotypes-of-heterotopic-ossification
#13
Devaveena Dey, Jana Bagarova, Sarah J Hatsell, Kelli A Armstrong, Lily Huang, Joerg Ermann, Ashley J Vonner, Yue Shen, Agustin H Mohedas, Arthur Lee, Elisabeth M W Eekhoff, Annelies van Schie, Marie B Demay, Charles Keller, Amy J Wagers, Aris N Economides, Paul B Yu
Fibrodysplasia ossificans progressiva (FOP), a congenital heterotopic ossification (HO) syndrome caused by gain-of-function mutations of bone morphogenetic protein (BMP) type I receptor ACVR1, manifests with progressive ossification of skeletal muscles, tendons, ligaments, and joints. In this disease, HO can occur in discrete flares, often triggered by injury or inflammation, or may progress incrementally without identified triggers. Mice harboring an Acvr1(R206H) knock-in allele recapitulate the phenotypic spectrum of FOP, including injury-responsive intramuscular HO and spontaneous articular, tendon, and ligament ossification...
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27881733/lysosomal-trafficking-regulator-lyst-links-membrane-trafficking-to-toll-like-receptor-mediated-inflammatory-responses
#14
Andreas Westphal, Weijia Cheng, Jinbo Yu, Guntram Grassl, Martina Krautkrämer, Otto Holst, Niko Föger, Kyeong-Hee Lee
Subcellular compartmentalization of receptor signaling is an emerging principle in innate immunity. However, the functional integration of receptor signaling pathways into membrane trafficking routes and its physiological relevance for immune responses is still largely unclear. In this study, using Lyst-mutant beige mice, we show that lysosomal trafficking regulator Lyst links endolysosomal organization to the selective control of toll-like receptor 3 (TLR3)- and TLR4-mediated proinflammatory responses. Consequently, Lyst-mutant mice showed increased susceptibility to bacterial infection and were largely resistant to endotoxin-induced septic shock...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27867020/a-randomized-dose-escalation-study-of-intravenous-baclofen-in%C3%A2-healthy-volunteers-clinical-tolerance-and-pharmacokinetics
#15
Natalie S Schmitz, Linda E Krach, Lisa D Coles, Usha Mishra, Suresh K Agarwal, James C Cloyd, Robert L Kriel
BACKGROUND: Abrupt discontinuation of baclofen can result in a potentially severe withdrawal syndrome. The current treatment for baclofen withdrawal is inadequate, resulting in a critical need to develop an alternative method to prevent or treat this withdrawal syndrome. OBJECTIVE: To evaluate the safety profile and pharmacokinetics of oral (PO) and investigational intravenous (IV) baclofen formulations at clinically relevant doses. DESIGN: Randomized, open-label, dose-escalation, crossover study...
November 17, 2016: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/27857494/osteofascial-compartment-pressure-measurement-in-closed-limb-injuries-whitesides-technique-revisited
#16
Rajendra Kumar Beniwal, Abhishek Bansal
INTRODUCTION: Regular monitoring of tissue compartmental pressures and hence a timely intervention in patients with impending compartment syndrome has been shown to prevent morbidity and permanent disability. MATERIAL AND METHODS: Intra-compartmental pressure in flexor compartment of forearm and various compartments of legs following recent trauma presenting within 6 h of injury was carried out in 30 subjects using Whitesides' technique and patients were classified into 3 categories for treatment purposes i...
October 2016: Journal of Clinical Orthopaedics and Trauma
https://www.readbyqxmd.com/read/27845481/unilateral-variation-in-extensor-digitorum-longus-muscle
#17
A Banerje, S Singh, K Raza, N Rani, S Kaler
During a routine dissection of an adult embalmed male cadaver for educational purpose in the department of anatomy at AIIMS, New Delhi, India, a rare unilateral variation of extensor digitorum longus (EDL) was found which is a muscle of anterior compartment of the leg. There was a split tendon of EDL muscle in the anterior compartment of left leg which became a common tendon in front of the ankle joint. This common tendon of EDL muscle again divided into four slips and were inserted in to the lateral four toes...
September 2016: La Clinica Terapeutica
https://www.readbyqxmd.com/read/27796667/lymphocyte-integrin-expression-differences-between-sirs-and-sepsis-patients
#18
D S Heffernan, S F Monaghan, Alfred Ayala
BACKGROUND: Systemic Inflammatory Response Syndrome (SIRS) and sepsis remain leading causes of death. Despite many similarities, the two entities are very distinct clinically and immunologically. T-Lymphocytes play a key pivotal role in the pathogenesis and ultimately outcome following both SIRS and sepsis. Integrins are essential in the trafficking and migration of lymphocytes. They also serve vital roles in efficient wound healing and clearance of infections. Here, we investigate whether integrin expression, specifically β1 (CD29) and β2 (CD18), are disrupted in SIRS and sepsis, and assess differences in integrin expression between these two critically ill clinical categories...
October 31, 2016: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/27756790/the-compartment-syndrome-is-the-intra-compartment-pressure-a-reliable-indicator-for-early-diagnosis
#19
Iftah Nudel, Luis Dorfmann, Gal deBotton
Compartment syndrome (CS) occurs when the pressure in an enclosed compartment increases due to tissue swelling or internal bleeding. As the intra-compartmental pressure (ICP) builds up, the blood flow to the tissue or the organ is compromised, resulting in ischemia, necrosis and damage to the nerves and other tissues. At the present there are no established diagnostic procedures, and clinical observations such as pain, paralysis and even compartment pressure monitoring are an unreliable determinant of the presence of the syndrome...
October 18, 2016: Mathematical Medicine and Biology: a Journal of the IMA
https://www.readbyqxmd.com/read/27537518/comparison-of-nirs-serum-biomarkers-and-muscle-damage-in-a-porcine-balloon-compression-model-of-acute-compartment-syndrome
#20
Steven C Budsberg, Michael S Shuler, Megan Hansen, Elizabeth Uhl, Brett A Freedman
BACKGROUND: Near-infrared spectroscopy (NIRS) has been shown to aid in the diagnosis of extremity acute compartment syndrome (ACS), offering continuous real-time capability to monitor perfusion in extremities. Porcine models of ACS have been developed to attempt to aid in the understanding of the development of ACS and provide better methods of diagnosing ACS. The objective of the present study was to assess and correlate NIRS, tibial intracompartmental pressure (TICP), tibial intracompartmental perfusion pressure (TIPP), serum markers of inflammation and muscle injury in a balloon compression model of ACS...
November 2016: Journal of Trauma and Acute Care Surgery
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