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when to halt systemic treatment

Edward M Gilbert, Weining David Xu
Heart failure (HF) in the United States represents a significant burden for patients and a tremendous strain on the healthcare system. Patients receiving a diagnosis of HF can be placed into 1 of 4 New York Heart Association (NYHA) functional classifications; the greatest proportion of patients are in the NYHA class II category, which is defined as patients having a slight limitation of physical activity but who are comfortable at rest, and for whom ordinary physical activity results in symptoms of HF. Because the severity of NYHA class II HF may be perceived as mild or unalarming by this definition, the urgency to treat this type of HF may be overlooked...
August 2017: Postgraduate Medicine
Saadeddine Saad, Bobbak Mansouri, Chad Housewright
Imiquimod activates the immune system when applied to a local area. We report a patient with a history of well-controlled myasthenia gravis who was prescribed imiquimod for lentigo maligna. Treatment was halted after 2 weeks when the patient reported itching and irritating sensations in his throat, consistent with previous myasthenia exacerbations. The symptoms improved once imiquimod use was discontinued. We advise clinicians to be cautious when prescribing imiquimod to a patient with a history of myasthenia gravis...
July 2017: Proceedings of the Baylor University Medical Center
Anneliese L Barth, Tatiana S P C de Magalhães, Ana Beatriz R Reis, Maria Lucia de Oliveira, Fernanda B Scalco, Nicolette C Cavalcanti, Daniel S E Silva, Danielle A Torres, Alessandra A P Costa, Carmem Bonfim, Roberto Giugliani, Juan C Llerena, Dafne D G Horovitz
Mucopolysaccharidosis type II (MPS II - Hunter syndrome) is an X-linked lysosomal storage disorder caused by a deficiency in the enzyme iduronate-2 sulfatase (I2S), leading to the accumulation of the glycosaminoglycans, affecting multiple organs and systems. Enzyme replacement therapy does not cross the blood brain barrier, limiting results in neurological forms of the disease. Another option of treatment for severe MPS, hematopoietic stem cell transplantation (HSCT) has become the treatment of choice for the severe form of MPS type I, since it can preserve neurocognition when performed early in the course of the disease...
September 2017: Molecular Genetics and Metabolism Reports
Holger Wemmelund
An abdominal aortic aneurysm (AAA) is an enlargement of the abdominal aorta. It is a common disease in the elderly, with a prevalence of 1-5%. An AAA is normally asymptomatic, and the diagnosis is often incidental, identified when a patient is examined for other conditions. The major risk of having an AAA is sudden rupture and death caused by massive hemorrhaging. As rupture risk increases with increasing AAA diameter, the current management strategies include regular imaging surveillance and elective repair before rupture occurs...
May 2017: Danish Medical Journal
Martin F J Perescis, Natasja de Bruin, Liesbeth Heijink, Chris Kruse, Lyudmila Vinogradova, Annika Lüttjohann, Gilles van Luijtelaar, Clementina M van Rijn
Cannabinoid CB1 antagonists have been investigated for possible treatment of e.g. obesity-related disorders. However, clinical application was halted due to their symptoms of anxiety and depression. In addition to these adverse effects, we have shown earlier that chronic treatment with the CB1 antagonist rimonabant may induce EEG-confirmed convulsive seizures. In a regulatory repeat-dose toxicity study violent episodes of "muscle spasms" were observed in Wistar rats, daily dosed with the CB1 receptor antagonist SLV326 during 5 months...
2017: PloS One
Ethan Hollingsworth, Jamil Khouri, Jaime Imitola
In recent years, there has been progress in understanding the etiology and immune mechanisms of multiple sclerosis (MS). however, for most, once the diagnosis is made, significant pathology is already present in the central nervous system (CNS), and in many, this leads to neurodegeneration, which accumulates in disability. although, the mechanisms of such progression are poorly understood, new data suggest lack of remyelination paired with dysfunction of neurons along with stem and progenitor cells as the basis and recent developmental studies suggest that cns repair processes share mechanisms with development...
June 2017: Expert Review of Neurotherapeutics
NamHuk Baek, Ok Won Seo, MinSung Kim, John Hulme, Seong Soo A An
Recently, increasing numbers of cell culture experiments with 3D spheroids presented better correlating results in vivo than traditional 2D cell culture systems. 3D spheroids could offer a simple and highly reproducible model that would exhibit many characteristics of natural tissue, such as the production of extracellular matrix. In this paper numerous cell lines were screened and selected depending on their ability to form and maintain a spherical shape. The effects of increasing concentrations of doxorubicin (DXR) on the integrity and viability of the selected spheroids were then measured at regular intervals and in real-time...
2016: OncoTargets and Therapy
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...
November 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
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