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CNS Infection

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141. Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation

Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove (...) one or more studies before adding more. Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care provider before participating. Read our for details. ClinicalTrials.gov Identifier: NCT02796755 Recruitment Status

2016 Clinical Trials

142. Inflammation-Induced CNS Glutamate Changes in Depression

Inflammation-Induced CNS Glutamate Changes in Depression Inflammation-Induced CNS Glutamate Changes in Depression - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. Inflammation-Induced CNS Glutamate Changes (...) antidepressant therapy. The goal of the proposed research is to test the hypothesis that inflammation alters behavior through increasing glutamate in specific brain regions, ultimately leading to behavioral changes. The proposed research is designed to determine the cause and effect relationship between inflammation and CNS glutamate as well as the relationship between CNS glutamate and specific symptoms. To accomplish these aims, investigators will administer a single infusion of either the tumor necrosis

2016 Clinical Trials

143. Safety Study of CN-105 Neuroprotective Peptide for Intracerebral Hemorrhage

Safety Study of CN-105 Neuroprotective Peptide for Intracerebral Hemorrhage Safety Study of CN-105 Neuroprotective Peptide for Intracerebral Hemorrhage - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. Safety (...) Study of CN-105 Neuroprotective Peptide for Intracerebral Hemorrhage The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our for details. ClinicalTrials.gov Identifier: NCT02670824 Recruitment Status : Completed First Posted : February 2, 2016 Last Update Posted : August 18, 2016 Sponsor: AegisCN LLC Information provided by (Responsible Party): AegisCN

2016 Clinical Trials

144. Intermittent High-Dose Lapatinib in Tandem With Capecitabine for HER2 Overexpressed/Amplified Metastatic Breast Cancer With Central Nervous System (CNS) Metastases

Intermittent High-Dose Lapatinib in Tandem With Capecitabine for HER2 Overexpressed/Amplified Metastatic Breast Cancer With Central Nervous System (CNS) Metastases Intermittent High-Dose Lapatinib in Tandem With Capecitabine for HER2 Overexpressed/Amplified Metastatic Breast Cancer With Central Nervous System (CNS) Metastases - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x (...) × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. Intermittent High-Dose Lapatinib in Tandem With Capecitabine for HER2 Overexpressed/Amplified Metastatic Breast Cancer With Central Nervous System (CNS) Metastases The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated

2016 Clinical Trials

145. Study of RXDX-101 in Children With Recurrent or Refractory Solid Tumors and Primary CNS Tumors, With or Without TRK, ROS1, or ALK Fusions

Study of RXDX-101 in Children With Recurrent or Refractory Solid Tumors and Primary CNS Tumors, With or Without TRK, ROS1, or ALK Fusions Study of RXDX-101 in Children With Recurrent or Refractory Solid Tumors and Primary CNS Tumors, With or Without TRK, ROS1, or ALK Fusions - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study (...) Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. Study of RXDX-101 in Children With Recurrent or Refractory Solid Tumors and Primary CNS Tumors, With or Without TRK, ROS1, or ALK Fusions The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care

2016 Clinical Trials

146. A Study of Lorlatinib in Advanced ALK and ROS1 Rearranged Lung Cancer With CNS Metastasis in the Absence of Measurable Extracranial Lesions

A Study of Lorlatinib in Advanced ALK and ROS1 Rearranged Lung Cancer With CNS Metastasis in the Absence of Measurable Extracranial Lesions A Study of Lorlatinib in Advanced ALK and ROS1 Rearranged Lung Cancer With CNS Metastasis in the Absence of Measurable Extracranial Lesions - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study (...) Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. A Study of Lorlatinib in Advanced ALK and ROS1 Rearranged Lung Cancer With CNS Metastasis in the Absence of Measurable Extracranial Lesions The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care

2016 Clinical Trials

147. Trial of CUDC-907 in Children and Young Adults With Relapsed or Refractory Solid Tumors, CNS Tumors, or Lymphoma

Trial of CUDC-907 in Children and Young Adults With Relapsed or Refractory Solid Tumors, CNS Tumors, or Lymphoma Trial of CUDC-907 in Children and Young Adults With Relapsed or Refractory Solid Tumors, CNS Tumors, or Lymphoma - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved (...) studies (100). Please remove one or more studies before adding more. Trial of CUDC-907 in Children and Young Adults With Relapsed or Refractory Solid Tumors, CNS Tumors, or Lymphoma The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care provider before participating. Read our for details. ClinicalTrials.gov

2016 Clinical Trials

148. Study of Lenalidomide With Vorinostat in Pediatric Patients With High Grade or Progressive CNS Tumors

Study of Lenalidomide With Vorinostat in Pediatric Patients With High Grade or Progressive CNS Tumors Study of Lenalidomide With Vorinostat in Pediatric Patients With High Grade or Progressive CNS Tumors - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please (...) remove one or more studies before adding more. Study of Lenalidomide With Vorinostat in Pediatric Patients With High Grade or Progressive CNS Tumors The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care provider before participating. Read our for details. ClinicalTrials.gov Identifier: NCT03050450 Recruitment

2016 Clinical Trials

149. A Study of Intravenous EEDVsMit in Children With Recurrent / Refractory Solid or CNS Tumours Expressing EGFR

A Study of Intravenous EEDVsMit in Children With Recurrent / Refractory Solid or CNS Tumours Expressing EGFR A Study of Intravenous EEDVsMit in Children With Recurrent / Refractory Solid or CNS Tumours Expressing EGFR - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (...) (100). Please remove one or more studies before adding more. A Study of Intravenous EEDVsMit in Children With Recurrent / Refractory Solid or CNS Tumours Expressing EGFR (ECREST) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care provider before participating. Read our for details. ClinicalTrials.gov

2016 Clinical Trials

150. Phase II Trial of Temsirolimus for Relapsed/Refractory Primary CNS Lymphoma. (PubMed)

Phase II Trial of Temsirolimus for Relapsed/Refractory Primary CNS Lymphoma. In this phase II study (NCT00942747), temsirolimus was tested in patients with relapsed or refractory primary CNS lymphoma (PCNSL).Immunocompetent adults with histologically confirmed PCNSL after experiencing high-dose methotrexate-based chemotherapy failure who were not eligible for or had experienced high-dose chemotherapy with autologous stem-cell transplant failure were included. The first cohort (n = 6) received (...) , 1.1 to 3.0 months). The most frequent Common Toxicity Criteria ≥ 3° adverse event was hyperglycemia in 11 (29.7%) patients, thrombocytopenia in eight (21.6%), infection in seven (19%), anemia in four (10.8%), and rash in three (8.1%). Fourteen blood/CSF pairs were collected in nine patients (10 pairs in five patients in the 25-mg cohort and four pairs in four patients in the 75-mg cohort). The mean maximum blood concentration was 292 ng/mL for temsirolimus and 37.2 ng/mL for its metabolite

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2016 Journal of Clinical Oncology

151. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. (PubMed)

, thrombocytopenia, anaemia, and febrile neutropenia or infections. 13 (6%) patients died of toxicity.With the limitations of a randomised phase 2 study design, the IELSG32 trial provides a high level of evidence supporting the use of MATRix combination as the new standard chemoimmunotherapy for patients aged up to 70 years with newly diagnosed primary CNS lymphoma and as the control group for future randomised trials.Associazione Italiana del Farmaco, Cancer Research UK, Oncosuisse, and Swiss National (...) Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Standard treatment for patients with primary CNS lymphoma remains to be defined. Active therapies are often associated with increased risk of haematological or neurological toxicity. In this trial, we addressed the tolerability and efficacy of adding

2016 The Lancet. Haematology

152. CNS vasculitis and stroke as a complication of DOCK8 deficiency: a case report. (PubMed)

by elevated levels of IgE antibody, eczema, and recurrent staphylococcal infections. DOCK8 deletion is associated with fatal CNS vasculitis. However, descriptions of such cases and their outcomes are scarce in the literature.This report describes a young female with a DOCK8 gene deletion presenting acutely with squint, fatigue and visual hallucinations. The patient was diagnosed as having neuritis of the third oculomotor nerve and encephalitis, which were thought to be related to her underlying immune (...) CNS vasculitis and stroke as a complication of DOCK8 deficiency: a case report. Primary immunodeficiency disorders associated with autoimmunity are poorly understood. Central nervous system (CNS) vasculitis can complicate the courses of such entities, but it is underappreciated. Deletion of the dedicator of cytokinesis 8 (DOCK8) gene is considered to be the autosomal recessive form of hyperimmunoglobulin E syndrome which is a rare type of primary immunodeficiency disease characterized

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2016 BMC Neurology

153. A Modified P1 Moiety Enhances in vitro Antiviral Activity against Various Multi-Drug-Resistant HIV-1 Variants and in vitro CNS Penetration Properties of a Novel Nonpeptidic Protease Inhibitor, GRL-10413. (PubMed)

of protease than in the case of darunavir. Moreover, the chlorine substituent in the P1 moiety interacts with protease in two distinct configurations. The present data demonstrate that GRL-10413 has desirable features for treating patients infected with wild-type and/or multidrug-resistant HIV-1 variants, with favorable CNS penetration capability, and that the newly modified P1 moiety may confer desirable features in designing novel anti-HIV-1 PIs.Copyright © 2016, American Society for Microbiology. All (...) A Modified P1 Moiety Enhances in vitro Antiviral Activity against Various Multi-Drug-Resistant HIV-1 Variants and in vitro CNS Penetration Properties of a Novel Nonpeptidic Protease Inhibitor, GRL-10413. We report here that GRL-10413, a novel nonpeptidic HIV-1 protease inhibitor (PI) containing a modified P1 moiety and a hydroxyethylamine sulfonamide isostere, is highly active against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC50] of 0.00035 to 0.0018

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2016 Antimicrobial Agents and Chemotherapy

154. Pediatric acquired CNS demyelinating syndromes: Features associated with multiple sclerosis. (PubMed)

Pediatric acquired CNS demyelinating syndromes: Features associated with multiple sclerosis. Approximately one-third of children with an acquired demyelinating syndrome (ADS) will be diagnosed with multiple sclerosis (MS), either at onset according to the 2010 McDonald criteria, or on the basis of clinical or MRI evidence of relapsing disease, in the majority of patients within 2-4 years. ADS in adolescents, female patients, and patients with polyfocal deficits is associated with the highest (...) likelihood of MS, while children with acute disseminated encephalomyelitis, those with documented preceding infection, and ADS presentation in young children more commonly portends a monophasic outcome. While pediatric MS associates with similar genetic risk alleles as have been documented in adult-onset MS, such associations are not diagnostically valuable at the individual level. The presence of antibodies directed against aquaporin-4 strongly supports a diagnosis of neuromyelitis optica, and should

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2016 Neurology

155. Sensing of HSV-1 by the cGAS–STING pathway in microglia orchestrates antiviral defence in the CNS (PubMed)

. Consistently, mice defective in cGAS or STING are highly susceptible to acute HSE. Although STING is redundant for cell-autonomous antiviral resistance in astrocytes and neurons, viral replication is strongly increased in neurons in STING-deficient mice. Interestingly, HSV-infected microglia confer STING-dependent antiviral activities in neurons and prime type I IFN production in astrocytes through the TLR3 pathway. Thus, sensing of HSV-1 infection in the CNS by microglia through the cGAS-STING pathway (...) Sensing of HSV-1 by the cGAS–STING pathway in microglia orchestrates antiviral defence in the CNS Herpes simplex encephalitis (HSE) is the most common form of acute viral encephalitis in industrialized countries. Type I interferon (IFN) is important for control of herpes simplex virus (HSV-1) in the central nervous system (CNS). Here we show that microglia are the main source of HSV-induced type I IFN expression in CNS cells and these cytokines are induced in a cGAS-STING-dependent manner

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2016 Nature communications

156. Highly efficient transduction of primary adult CNS and PNS neurons (PubMed)

Highly efficient transduction of primary adult CNS and PNS neurons Delivery and expression of recombinant genes, a key methodology for many applications in biological research, remains a challenge especially for mature neurons. Here, we report easy, highly efficient and well tolerated transduction of adult peripheral and central neuronal populations of diverse species in culture using VSV-G pseudo-typed, recombinant baculovirus (BacMam). Transduction rates of up to 80% were reliably achieved (...) at high multiplicity of infection without apparent neuro-cytopathic effects. Neurons could be transduced either shortly after plating or after several days in culture. Co-incubation with two different baculoviruses attained near complete co-localization of fluorescent protein expression, indicating multigene delivery. Finally, evidence for functional protein expression is provided by means of cre-mediated genetic recombination and neurite outgrowth assays. Recombinant protein was already detected

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2016 Scientific reports

157. Alcohol intake alters immune responses and promotes CNS viral persistence in mice (PubMed)

Alcohol intake alters immune responses and promotes CNS viral persistence in mice Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral (...) persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n=94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60days post-infection and continued

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2016 Behavioural brain research

158. GLT-1-Dependent Disruption of CNS Glutamate Homeostasis and Neuronal Function by the Protozoan Parasite Toxoplasma gondii (PubMed)

GLT-1-Dependent Disruption of CNS Glutamate Homeostasis and Neuronal Function by the Protozoan Parasite Toxoplasma gondii The immune privileged nature of the CNS can make it vulnerable to chronic and latent infections. Little is known about the effects of lifelong brain infections, and thus inflammation, on the neurological health of the host. Toxoplasma gondii is a parasite that can infect any mammalian nucleated cell with average worldwide seroprevalence rates of 30%. Infection by Toxoplasma (...) is characterized by the lifelong presence of parasitic cysts within neurons in the brain, requiring a competent immune system to prevent parasite reactivation and encephalitis. In the immunocompetent individual, Toxoplasma infection is largely asymptomatic, however many recent studies suggest a strong correlation with certain neurodegenerative and psychiatric disorders. Here, we demonstrate a significant reduction in the primary astrocytic glutamate transporter, GLT-1, following infection with Toxoplasma

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2016 PLoS pathogens

159. Development of an Orally Available and Central Nervous System (CNS)-Penetrant Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) Inhibitor with Minimal Human Ether-à-go-go-Related Gene (hERG) Activity for the Treatment of Toxoplasmosis (PubMed)

Development of an Orally Available and Central Nervous System (CNS)-Penetrant Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) Inhibitor with Minimal Human Ether-à-go-go-Related Gene (hERG) Activity for the Treatment of Toxoplasmosis New therapies are needed for the treatment of toxoplasmosis, which is a disease caused by the protozoan parasite Toxoplasma gondii. To this end, we previously developed a potent and selective inhibitor (compound 1) of Toxoplasma gondii calcium (...) -dependent protein kinase 1 (TgCDPK1) that possesses antitoxoplasmosis activity in vitro and in vivo. Unfortunately, 1 has potent human ether-a-go-go-related gene (hERG) inhibitory activity, associated with long Q-T syndrome, and consequently presents a cardiotoxicity risk. Here, we describe the identification of an optimized TgCDPK1 inhibitor 32, which does not have a hERG liability and possesses a favorable pharmacokinetic profile in small and large animals. 32 is CNS-penetrant and highly effective

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2016 Journal of medicinal chemistry

160. Activated GL7<sup>+</sup> B cells are maintained within the inflamed CNS in the absence of follicle formation during viral encephalomyelitis. (PubMed)

Activated GL7+ B cells are maintained within the inflamed CNS in the absence of follicle formation during viral encephalomyelitis. Central nervous system (CNS) inflammation associated with viral infection and autoimmune disease results in the accumulation of B cells in various differentiation stages. However, the contribution between peripheral and CNS activation remains unclear. During gliatropic coronavirus induced encephalomyelitis, accumulation of protective antibody secreting (...) confined to the perivascular space and meninges, with only rare B cell clusters, while isotype-switched B cells localized to parenchymal areas. Although ectopic follicle formation was not observed, more differentiated B cell subsets within the CNS expressed the germinal center marker GL7, albeit at lower levels than CLN counterparts. During chronic infection, CNS IgDint and IgD- B cell subsets further displayed sustained markers of proliferation and CD4 T cell help, which were only transiently

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2016 Brain, behavior, and immunity

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