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when to halt systemic treatment

Mary Ho, Wilson W K Yip, Vesta C K Chan, Alvin L Young
PURPOSE: To describe a case of incontinentia pigmenti with proliferative retinopathy successfully treated by combination of repeated retinal laser photocoagulation and intravitreal ranibizumab injection. METHODS: Single interventional case report of a 4-year-old girl, known case of incontientia pigmenti, first screened at the age of two, presented with proliferative retinopathy. Sole treatment by panretinal laser photocoagulation failed to control the progression of retinal neovascularization...
July 28, 2016: Retinal Cases & Brief Reports
L Kahl, J Patel, M Layton, M Binks, K Hicks, G Leon, E Hachulla, D Machado, D Staumont-Sallé, M Dickson, L Condreay, L Schifano, S Zamuner, R F van Vollenhoven
We aimed to evaluate the pharmacodynamics, efficacy, safety and tolerability of the JAK1 inhibitor GSK2586184 in adults with systemic lupus erythematosus (SLE). In this adaptive, randomized, double-blind, placebo-controlled study, patients received oral GSK2586184 50-400 mg, or placebo twice daily for 12 weeks. Primary endpoints included interferon-mediated messenger RNA transcription over time, changes in Safety of Estrogen in Lupus National Assessment-SLE Disease Activity Index score, and number/severity of adverse events...
April 6, 2016: Lupus
Rachel A Sheridan, Hom-Lay Wang, Robert Eber, Tae-Ju Oh
Periodontitis is an inflammatory condition of the periodontium that leads to destruction of the supporting structures of the tooth, including loss of attachment and alveolar bone. A clinician's first line of treatment for periodontitis is traditionally mechanical periodontal therapy, including oral hygiene instructions together with scaling and root planing. How- ever, it has been shown that mechanical therapy may not always be effective in halting disease. Adjunctive chemotherapeutics, such as systemic antibiotics or host-modulating agents, may improve the treatment outcome of periodontitis...
October 2015: Journal of the International Academy of Periodontology
Amy L Strong, Annie C Bowles, Rachel M Wise, Joseph P Morand, Maria F Dutreil, Jeffrey M Gimble, Bruce A Bunnell
Multiple sclerosis is an autoimmune disease that affects the white matter of the central nervous system and involves inflammation and demyelination. The recent advances in our understanding of adipose-derived stromal/stem cells (ASCs) and the utilization of these cells in clinical settings to treat diseases have made it essential to identify the most effective ASCs for therapy. Studies have not yet investigated the impact of obesity on the therapeutic efficacy of ASCs. Obesity is characterized by adipocyte hyperplasia and hypertrophy and can extend to metabolic and endocrine dysfunction...
March 2016: Stem Cells
Long Juan, Zhao Xiao, Yun Song, Zhang Zhijian, Jin Jing, Yu Kun, Hao Yuna, Dai Dongfa, Ding Lili, Tan Liuxin, Liang Fei, Liu Nan, Yuan Fang, Sun Yuying, Xi Yongzhi
Current clinically available treatments for rheumatoid arthritis (RA) fail to cure the disease or unsatisfactorily halt disease progression. To overcome these limitations, the development of therapeutic DNA vaccines and boosters may offer new promising strategies. Because type II collagen (CII) as a critical autoantigen in RA and native chicken type II collagen (nCCII) has been used to effectively treat RA, we previously developed a novel therapeutic DNA vaccine encoding CCII (pcDNA-CCOL2A1) with efficacy comparable to that of the current "gold standard", methotrexate(MTX)...
2015: Human Vaccines & Immunotherapeutics
Sarah Rae Easter, David E Cantonwine, Chloe A Zera, Kee-Hak Lim, Samuel I Parry, Thomas F McElrath
BACKGROUND: Despite decades of research, and much progress in discernment of biomarkers in the maternal circulation, the pathogenesis of preeclampsia (PE) remains elusive. The pathophysiology of PE is believed to involve aberrant placentation and an associated increase in systemic inflammation. In this conceptualization, PE becomes more likely when the level of systemic inflammatory burden inherent in pregnancy itself exceeds the maternal capacity to compensate for this additional stress...
March 2016: American Journal of Obstetrics and Gynecology
Emma Board-Davies, Rachael Moses, Alastair Sloan, Phil Stephens, Lindsay C Davies
UNLABELLED: The oral cavity possesses a diverse microflora, yet recurrent infections within healthy individuals are rare. Wound healing within the buccal mucosa is preferential, potentially because of the presence of oral mucosal lamina propria-progenitor cells (OMLP-PCs). In addition to their multipotency, OMLP-PCs demonstrate potent immunosuppressive properties. The present study investigated whether OMLP-PCs possess antibacterial properties, directly interacting with microorganisms and contributing to the maintenance of a balanced oral microflora...
November 2015: Stem Cells Translational Medicine
Julia A E Radic, Ian Beauprie, Paula Chiasson, Zelma H T Kiss, Robert M Brownstone
BACKGROUND: Chronic motor cortex stimulation (MCS) has been used to treat medically refractory neuropathic pain over the past 20 years. We investigated this procedure using a prospective multicentre randomized blinded crossover trial. METHODS: Twelve subjects with three different neuropathic pain syndromes had placement of MCS systems after which they were randomized to receive low ("subtherapeutic") or high ("therapeutic") stimulation for 12 weeks, followed by a crossover to the other treatment group for 12 weeks...
November 2015: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
Kurt Giles, David B Berry, Carlo Condello, Ronald C Hawley, Alejandra Gallardo-Godoy, Clifford Bryant, Abby Oehler, Manuel Elepano, Sumita Bhardwaj, Smita Patel, B Michael Silber, Shenheng Guan, Stephen J DeArmond, Adam R Renslo, Stanley B Prusiner
Because no drug exists that halts or even slows any neurodegenerative disease, developing effective therapeutics for any prion disorder is urgent. We recently reported two compounds (IND24 and IND81) with the 2-aminothiazole (2-AMT) chemical scaffold that almost doubled the incubation times in scrapie prion-infected, wild-type (wt) FVB mice when given in a liquid diet. Remarkably, oral prophylactic treatment with IND24 beginning 14 days prior to intracerebral prion inoculation extended survival from ∼120 days to over 450 days...
October 2015: Journal of Pharmacology and Experimental Therapeutics
Huiming Xu, Yonghui Wang, Zuping He, Hao Yang, Wei-Qiang Gao
Degeneration or loss of GABAergic neurons frequently may lead to many neuropsychiatric disorders such as epilepsy and autism spectrum disorders. So far no clinically effective therapies can slow and halt the progression of these diseases. Cell-replacement therapy is a promising strategy for treatment of these neuropsychiatric diseases. Although increasing evidence showed that mammalian somatic cells can be directly converted into functional neurons using specific transcription factors or miRNAs via virus delivery, the application of these induced neurons is potentially problematic, due to integration of vectors into the host genome, which results in the disruption or dysfunction of nearby genes...
August 3, 2015: Cell Cycle
Hani J Alturkmani, Ziyan Y Pessetto, Andrew K Godwin
INTRODUCTION: Gastrointestinal stromal tumor (GIST) is the most common nonepithelial malignancy of the GI tract. With the discovery of KIT and later platelet-derived growth factor α (PDGFRA) gain-of-function mutations as factors in the pathogenesis of the disease, GIST was the quintessential model for targeted therapy. Despite the successful clinical use of imatinib mesylate, a selective receptor tyrosine kinase (RTK) inhibitor that targets KIT, PDGFRA and BCR-ABL, we still do not have treatment for the long-term control of advanced GIST...
2015: Expert Opinion on Investigational Drugs
Ming Zhang, Gang Yu, Brian Chan, Joshua T Pearson, Palaniswami Rathanaswami, John Delaney, Ai Ching Lim, John Babcook, Hailing Hsu, Marc A Gavin
OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is driven in part by chronic B and T lymphocyte hyperresponsiveness to self antigens. A deficiency of interleukin-21 (IL-21) or IL-21 receptor (IL-21R) in mice dramatically reduces inflammation and B and T cell activation in models of autoimmunity, including SLE. However, whether IL-21 is essential for the maintenance and amplification of preestablished inflammation has not been widely examined in various animal models...
October 2015: Arthritis & Rheumatology
Konstantinos C Koskinas, Stephan Windecker, Lorenz Räber
Coronary atherosclerosis has been considered a chronic disease characterized by ongoing progression in response to systemic risk factors and local pro-atherogenic stimuli. As our understanding of the pathobiological mechanisms implicated in atherogenesis and plaque progression is evolving, effective treatment strategies have been developed that led to substantial reduction of the clinical manifestations and acute complications of coronary atherosclerotic disease. More recently, intracoronary imaging modalities have enabled detailed in vivo quantification and characterization of coronary atherosclerotic plaque, serial evaluation of atherosclerotic changes over time, and assessment of vascular responses to effective anti-atherosclerotic medications...
February 2016: Trends in Cardiovascular Medicine
Weifeng Huang, Chunjing Lu, Yong Wu, Shou Ouyang, Yuanzhong Chen
BACKGROUND: T-type Ca(2+) channels are often aberrantly expressed in different human cancers and participate in the regulation of cell cycle progression, proliferation and death. METHODS: RT-PCR, Q-PCR, western blotting and whole-cell patch-clamp recording were employed to assess the expression of T-type Ca(2+) channels in leukemia cell lines. The function of T-type Ca(2+) channels in leukemia cell growth and the possible mechanism of the effect of T-type Ca(2+) channel antagonists on cell proliferation and apoptosis were examined in T-lymphoma cell lines...
2015: Journal of Experimental & Clinical Cancer Research: CR
Alessandro Torgovnick, Björn Schumacher
DNA damage has been long recognized as causal factor for cancer development. When erroneous DNA repair leads to mutations or chromosomal aberrations affecting oncogenes and tumor suppressor genes, cells undergo malignant transformation resulting in cancerous growth. Genetic defects can predispose to cancer: mutations in distinct DNA repair systems elevate the susceptibility to various cancer types. However, DNA damage not only comprises a root cause for cancer development but also continues to provide an important avenue for chemo- and radiotherapy...
2015: Frontiers in Genetics
Marieke Biegstraaten, Reynir Arngrímsson, Frederic Barbey, Lut Boks, Franco Cecchi, Patrick B Deegan, Ulla Feldt-Rasmussen, Tarekegn Geberhiwot, Dominique P Germain, Chris Hendriksz, Derralynn A Hughes, Ilkka Kantola, Nesrin Karabul, Christine Lavery, Gabor E Linthorst, Atul Mehta, Erica van de Mheen, João P Oliveira, Rossella Parini, Uma Ramaswami, Michael Rudnicki, Andreas Serra, Claudia Sommer, Gere Sunder-Plassmann, Einar Svarstad, Annelies Sweeb, Wim Terryn, Anna Tylki-Szymanska, Camilla Tøndel, Bojan Vujkovac, Frank Weidemann, Frits A Wijburg, Peter Woolfson, Carla E M Hollak
INTRODUCTION: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed to define European consensus recommendations for the initiation and cessation of ERT in patients with FD. METHODS: A Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15)...
2015: Orphanet Journal of Rare Diseases
Juha Punnonen, James L Miller, Timothy J Collier, Jeffrey R Spencer
Parkinson's disease (PD) is a neurodegenerative disease affecting more than a million people in the USA alone. While there are effective symptomatic treatments for PD, there is an urgent need for new therapies that slow or halt the progressive death of dopaminergic neurons. Significant progress has been made in understanding the pathophysiology of PD, which has substantially facilitated the discovery efforts to identify novel drugs. The tissue-protective erythropoietin (EPO) receptor, EPOR/CD131, has emerged as one promising target for disease-modifying therapies...
2015: Current Topics in Medicinal Chemistry
John L Humm, Oliver Sartor, Chris Parker, Oyvind S Bruland, Roger Macklis
The element radium (Ra) was discovered by the Curies in 1898 and within a decade was in broad scientific testing for the management of several forms of cancer. The compound was known to give rise to a series of both high-energy particulate and penetrating γ-emissions. The latter found an important role in early 20th century brachytherapy applications, but the short-range α-particles seemed much less useful. Although highly cytotoxic when released within a few cell diameters of critical cell nuclei, the dense double-strand break damage was poorly repaired, and concerns regarding treatment-related toxicities and secondary malignancies halted clinical development...
April 1, 2015: International Journal of Radiation Oncology, Biology, Physics
Kenton H Fibel, Howard J Hillstrom, Brian C Halpern
Osteoarthritis (OA) is the most common type of arthritis found in the United States' population and is also the most common disease of joints in adults throughout the world with the knee being the most frequently affected of all joints. As the United States' population ages along with the increasing trends in obesity prevalence in other parts of the world, it is expected that the burden of OA on the population, healthcare system, and overall economy will continue to increase in the future without making major improvements in managing knee OA...
February 16, 2015: World Journal of Clinical Cases
John W Wright, Joseph W Harding
Alzheimer's disease (AD) is a progressive neurodegenerative disease increasing in frequency as life expectancy of the world's population increases. There are an estimated 5 million diagnosed AD patients in the U.S. and 16 million worldwide with no adequate treatment presently available. New therapeutic approaches are needed to slow, and hopefully reverse, disease progression. This review summarizes available information regarding an overlooked therapeutic target that may offer a treatment to slow and hopefully halt AD, namely the hepatocyte growth factor (HGF)/c-Met receptor system...
2015: Journal of Alzheimer's Disease: JAD
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