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Intrathecal drug therapy

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https://www.readbyqxmd.com/read/28628492/complete-remission-of-intrathecal-metastases-with-lorlatinib-therapy-in-a-heavily-pretreated-alk-positive-lung-cancer-patient
#1
Maximilian J Hochmair, Sophia Schwab, Helmut Prosch
Patients with lung cancer who show EML4-ALK translocation are routinely treated with ALK tyrosine kinase inhibitors, although in the majority of cases, these patients develop resistance over time. The central nervous system is a common of site of recurrence in this population, which calls for next-generation drugs that can penetrate into the brain and achieve clinically meaningful central nervous system activity. Here, I report the case of a female patient diagnosed with adenocarcinoma of the lung in 2005, at the age of 46 years, who underwent lobectomy and then experienced a series of progression episodes 6 years later...
June 16, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28573049/biphalin-a-dimeric-enkephalin-alleviates-lps-induced-activation-in-rat-primary-microglial-cultures-in-opioid-receptor-dependent-and-receptor-independent-manners
#2
Katarzyna Popiolek-Barczyk, Anna Piotrowska, Wioletta Makuch, Joanna Mika
Neuropathic pain is relatively less responsive to opioids than other types of pain, which is possibly due to a disrupted opioid system partially caused by the profound microglial cell activation that underlines neuroinflammation. We demonstrated that intrathecally injected biphalin, a dimeric enkephalin analog, diminished symptoms of neuropathy in a preclinical model of neuropathic pain in rats (CCI, chronic constriction injury of the sciatic nerve) at day 12 postinjury. Using primary microglial cell cultures, we revealed that biphalin did not influence cell viability but diminished NO production and expression of Iba1 in LPS-stimulated cells...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28561813/therapeutic-approaches-for-spinal-muscular-atrophy-sma
#3
REVIEW
M Scoto, R S Finkel, E Mercuri, F Muntoni
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder characterized by progressive muscle wasting and loss of muscle function due to severe motor neuron dysfunction, secondary to mutations in the survival motor neuron 1 (SMN1) gene. A second neighboring centromeric gene, SMN2, is intact in all patients but contains a C-to-T variation in exon 7 that affects a splice enhancer and determines exclusion of exon 7 in the majority of its transcript, leading to an unstable protein that cannot substitute for mutant SMN1...
May 31, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28529027/management-of-postneurosurgical-meningitis-narrative-review
#4
REVIEW
Khetam Hussein, Roni Bitterman, Ben Shofty, Mical Paul, Ami Neuberger
BACKGROUND: Infections complicating neurosurgery pose unacceptable mortality and morbidity. AIMS: To summarize what is known about the epidemiology, diagnosis and treatment of post-neurosurgical meningitis (PNM). SOURCES: PubMed, references of identified studies and reviews, and personal experience when evidence was lacking. CONTENT: The incidence and pathogen distribution of PNM is highly variable. A shift towards Gram-negative bacteria has been observed with use of antibiotic prophylaxis and antibiotic-coated devices directed mainly against Gram-positive bacteria...
May 18, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28500900/treatment-of-refractory-epilepsy-patients-with-autologous-mesenchymal-stem-cells-reduces-seizure-frequency-an-open-label-study
#5
Fedor Hlebokazov, Tatiana Dakukina, Svetlana Ihnatsenko, Svetlana Kosmacheva, Michael Potapnev, Antos Shakhbazau, Natalia Goncharova, Michael Makhrov, Pavel Korolevich, Nikolai Misyuk, Victoria Dakukina, Irina Shamruk, Elena Slobina, Sergei Marchuk
PURPOSE: Existing anti-epileptic drugs (AED) have limited efficiency in many patients, necessitating the search for alternative approaches such as stem cell therapy. We report the use of autologous patient-derived mesenchymal stem cells (MSC) as a therapeutic agent in symptomatic drug-resistant epilepsy in a Phase I open label clinical trial (registered as NCT02497443). PATIENTS AND METHODS: The patients received either standard treatment with AED (control group), or AED supplemented with single intravenous administration of undifferentiated autologous MSC (target dose of 1×10(6)cells/kg), followed by a single intrathecal injection of neurally induced autologous MSC (target dose of 0...
May 10, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28460120/post-neonatal-tetanus-in-a-picu-of-a-developing-economy-intensive-care-needs-outcome-and-predictors-of-mortality
#6
Suresh Kumar Angurana, Muralidharan Jayashree, Arun Bansal, Sunit Singhi, Karthi Nallasamy
Objectives: To evaluate pediatric intensive care unit (PICU) needs, outcome and predictors of mortality in post-neonatal tetanus. Materials and methods: Review of 30 consecutive post-neonatal tetanus cases aged 1 months to 12 years admitted to a PICU in north India over a period of 10 years (January 2006 to December 2015). Results: Chronic suppurative otitis media was the commonest portal of entry. All received tetanus toxoid, human tetanus immunoglobulin (HTIG) and appropriate antibiotics; 7 (23...
April 27, 2017: Journal of Tropical Pediatrics
https://www.readbyqxmd.com/read/28458952/intrathecal-baclofen-pump-infection-treated-by-adjunct-intrareservoir-teicoplanin-instillation
#7
Rovlias Aristedis, Papoutsakis Dimitrios, Paidakakos Nikolaos, Blionas Alexandros
BACKGROUND: The delivery of intrathecal baclofen via pumps is gaining increasing use in the management of intractable spasticity. One of the rare but devastating complications of this method is infection. In the majority of cases, removal of the device is required, despite appropriate intravenous antibiotic therapy. We report a case that highlights the use of intrareservoir teicoplanin to achieve sterilization of the infected pump system in a patient in whom removal of the pump was not an easy option...
2017: Surgical Neurology International
https://www.readbyqxmd.com/read/28444098/the-cerebrospinal-fluid-in-multiple-sclerosis-far-beyond-the-bands
#8
Renan Barros Domingues, Gustavo Bruniera Peres Fernandes, Fernando Brunale Vilela de Moura Leite, Charles Peter Tilbery, Rodrigo Barbosa Thomaz, Gisele Sampaio Silva, Cristóvão Luis Pitangueira Mangueira, Carlos Augusto Senne Soares
The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency...
January 2017: Einstein
https://www.readbyqxmd.com/read/28431478/successful-treatment-of-multidrug-resistant-acinetobacter-baumannii-meningitis-with-ampicillin-sulbactam-in-primary-hospital
#9
Leitao Sun, Xiaohong Wang, Zefu Li
INTRODUCTION: Acinetobacter baumannii nosocomial infections, especially those due to multi-drug resistant strains, are increasingly detected. We want to find the effective treatment measures about multi-resistant Acinetobacter baumannii infections through this research. METHODOLOGY: The clinical features and the outcomes of twelve cases of nosocomial Acinetobacter baumannii meningitis treated with ampicillin sulbactam and intrathecal use of amikacin are reported in primary hospital...
April 21, 2017: British Journal of Neurosurgery
https://www.readbyqxmd.com/read/28431428/computational-and-in-vitro-experimental-investigation-of-intrathecal-drug-distribution-parametric-study-of-the-effect-of-injection-volume-cerebrospinal-fluid-pulsatility-and-drug-uptake
#10
Kevin M Tangen, Roxanne Leval, Ankit I Mehta, Andreas A Linninger
BACKGROUND: Intrathecal drug delivery is an attractive option to circumvent the blood-brain barrier for pain management through its increased efficacy of pain relief, reduction in adverse side effects, and cost-effectiveness. Unfortunately, there are limited guidelines for physicians to choose infusion or drug pump settings to administer therapeutic doses to specific regions of the spine or the brain. Although empiric trialing of intrathecal drugs is critical to determine the sustained side effects, currently there is no inexpensive in vitro method to guide the selection of spinal drug delivery parameters...
May 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28400376/therapy-reduction-in-patients-with-down-syndrome-myeloid-leukemia-the-international-ml-ds-2006-trial
#11
Madita Uffmann, Mareike Rasche, Martin Zimmermann, Christine von Neuhoff, Ursula Creutzig, Michael Dworzak, Lenie Scheffers, Henrik Hasle, C Michel Zwaan, Dirk Reinhardt, Jan-Henning Klusmann
Children with Down syndrome and myeloid leukemia (ML-DS) have a superior outcome compared to non-DS patients, but suffer from higher constitutional susceptibility to cytotoxic drugs. We analyzed the outcome of 170 pediatric patients with ML-DS enrolled in the prospective, multi-center, open-label, non-randomized ML-DS 2006 trial, by the NOPHO, DCOG and AML-BFM study groups. In comparison to the historical control arm (reduced intensity protocol for ML-DS patients from the AML-BFM 98 trial) treatment intensity was reduced by lowering the cumulative dose of etoposide (950 mg/m(2) to 450 mg/m(2)) and intrathecal CNS-prophylaxis while omitting maintenance therapy...
April 11, 2017: Blood
https://www.readbyqxmd.com/read/28340041/bleeding-complications-in-patients-undergoing-intrathecal-drug-delivery-system-implantation
#12
Nafisseh S Warner, Markus A Bendel, Matthew A Warner, Jacob J Strand, Halena M Gazelka, Bryan C Hoelzer, William D Mauck, Tim J Lamer, Daryl J Kor, Susan M Moeschler
Introduction.:  Intrathecal drug delivery systems (IDDSs) have dramatically improved analgesia and the functional status of cancer patients and those with chronic pain states. However, given the close proximity to the neuraxis and frequent concomitant use of antiplatelet or anticoagulant medications, this intervention is not without risk. The goal of this investigation was to determine the incidence of bleeding complications following IDDS placement. Methods.:  This is a retrospective review from 2005 through 2014 of adult patients undergoing IDDS implantation or revision at a tertiary care center...
March 3, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28296770/evaluation-of-intrathecal-drug-delivery-system-for-intractable-pain-in-advanced-malignancies-a-prospective-cohort-study
#13
Shuyue Zheng, Liangliang He, Xiaohui Yang, Xiuhua Li, Zhanmin Yang
Pain is prevalent in advanced malignancies; however, some patients cannot get adequate pain relief by conservative routes of analgesic administration or experience serious side effects related to high dose of opioids. For those who have exhausted multimodal conservative analgesic, intrathecal drug delivery is an alternative intervention for truly effective pain management. The objective of this study was to evaluate the clinical efficacy and safety of intrathecal drug delivery system (IDDS) for the treatment of intractable pain in advanced cancer patients...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28271991/new-therapy-for-spinal-muscular-atrophy-offers-modest-bang-for-pharamaceutical-buck
#14
Thomas Morrow
Spinraza is a breakthrough, no doubt. It is a survival SMN-2-directed antisense oligonucleotide indicated for the treatment of SMA in pediatric and adult patients and is administered by injections into the spinal fluid (intrathecally). But it is another ultraexpensive drug, and the evidence so far points to a modest improvement in motor milestones.
February 2017: Managed Care
https://www.readbyqxmd.com/read/28230014/nimotuzumab-treatment-and-outcome-analysis-in-patients-with-leptomeningeal-metastasis-from-nonsmall-cell-lung-cancer
#15
Yanfang Ju, Jinliang Wang, Shengjie Sun, Shunchang Jiao
OBJECTIVE: Leptomeningeal metastasis (LM) leades a devastating consequence in patients with nonsmall cell lung cancer(NSCLC). Treatment is very limited for patients with LM. We introduced to use nimotuzumab (also known as h-R3) combined with methotrexate for treating LM in NSCLC patients. PATIENTS AND METHODS: In the present report, twenty patients with LM of NSCLC were included, and the clinicopathology information and outcomes after treatment were analyzed. RESULTS: All the twenty patients with LM were lung adenocarcinoma...
December 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28212183/cxcl12-cxcr4-signaling-contributes-to-the-pathogenesis-of-opioid-tolerance-a-translational-study
#16
Chih-Peng Lin, Kai-Hsiang Kang, Huang-Ju Tu, Ming-Yueh Wu, Tzu-Hung Lin, Houng-Chi Liou, Wei-Zen Sun, Wen-Mei Fu
BACKGROUND: Long-term opioid therapy for chronic pain may lead to analgesic tolerance, especially when administered intrathecally, thus preventing adequate pain relief. Discovering drug targets to treat opioid tolerance using a mechanism-based approach targeting opioid-induced neuroinflammation provides new therapeutic opportunities. In this study, we provide translational evidence that CXCL12/CXCR4 signaling contributes to the pathogenesis of opioid tolerance. METHODS: The CXCL12 levels in the cerebrospinal fluid of opioid-tolerant patients were compared with those of opioid-naive subjects...
March 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28156637/complications-of-intrathecal-pump-therapy-in-malignancy-related-pain
#17
Egidio Del Fabbro
102 Background: Intrathecal pumps (ITP) are used to manage severe malignancy related pain by delivering analgesics directly into the cerebrospinal fluid, in theory allowing for a reduced opioid dose and fewer complications. Although there is literature to support efficacy in patients with cancer, including improved survival, this mode of drug delivery also carries a risk of serious complications. Reports of complications in non-malignant pain suggest the risks and mortality related to ITP may be under-appreciated and that injury and liability occur with both ITP placement and ITP maintenance...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28105588/nogo-a-antibodies-for-progressive-multiple-sclerosis
#18
Benjamin V Ineichen, Patricia S Plattner, Nicolas Good, Roland Martin, Michael Linnebank, Martin E Schwab
Most of the current therapies, as well as many of the clinical trials, for multiple sclerosis (MS) target the inflammatory autoimmune processes, but less than 20% of all clinical trials investigate potential therapies for the chronic progressive disease stage of MS. The latter is responsible for the steadily increasing disability in many patients, and there is an urgent need for novel therapies that protect nervous system tissue and enhance axonal growth and/or remyelination. As outlined in this review, solid pre-clinical data suggest neutralization of the neurite outgrowth inhibitor Nogo-A as a potential new way to achieve both axonal and myelin repair...
January 19, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28045655/practical-aspects-of-the-use-of-intrathecal-chemotherapy
#19
Raquel Olmos-Jiménez, Alberto Espuny-Miró, Carlos Cárceles Rodríguez, María Sacramento Díaz-Carrasco
INTRODUCTION: Intrathecal chemotherapy is frequently used in clinical practice for treatment and prevention of neoplastic meningitis. Despite its widespread use, there is little information about practical aspects such as the volume of drug to be administered or its preparation and administration. OBJECTIVE: To conduct a literature review about practical aspects of the use of intrathecal chemotherapy. MATERIALS: Search in PubMed/ Medline using the terms "chemotherapy AND intrathecal", analysis of secondary and tertiary information sources...
January 1, 2017: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/28042914/the-polyanalgesic-consensus-conference-pacc-recommendations-for-intrathecal-drug-delivery-guidance-for-improving-safety-and-mitigating-risks
#20
REVIEW
Timothy R Deer, Jason E Pope, Salim M Hayek, Tim J Lamer, Ilir Elias Veizi, Michael Erdek, Mark S Wallace, Jay S Grider, Robert M Levy, Joshua Prager, Steven M Rosen, Michael Saulino, Tony L Yaksh, Jose A De Andrés, David Abejon Gonzalez, Jan Vesper, Stefan Schu, Brian Simpson, Nagy Mekhail
INTRODUCTION: Intrathecal therapy is an important part of the pain treatment algorithm for chronic disease states. The use of this option is a viable treatment strategy, but it is inherent for pain physicians to understand risk assessment and mitigation. In this manuscript, we explore evidence and mitigating strategies to improve safety with intrathecal therapy. METHODS: A robust literature search was performed covering January 2011 to October 9, 2016, in PubMed, Embase, MEDLINE, Biomed Central, Google Scholar, Current Contents Connect, and International Pharmaceutical Abstracts...
February 2017: Neuromodulation: Journal of the International Neuromodulation Society
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