DNA Damage Response in Cisplatin-Induced Nephrotoxicity

PubMed Central

Zhu, Shiyao; Pabla, Navjotsingh; Tang, Chengyuan; He, Liyu; Dong, Zheng

2015-01-01

Cisplatin and its derivatives are widely used chemotherapeutic drugs for cancer treatment. However, they have debilitating side-effects in normal tissues and induce ototoxicity, neurotoxicity, and nephrotoxicity. In kidneys, cisplatin preferentially accumulates in renal tubular cells causing tubular cell injury and death, resulting in acute kidney injury (AKI). Recent studies have suggested that DNA damage and the associated DNA damage response (DDR) is an important pathogenic mechanism of AKI following cisplatin treatment. Activation of DDR may lead to cell cycle arrest and DNA repair for cell survival or, in the presence of severe injury, kidney cell death. Modulation of DDR may provide novel renoprotective strategies for cancer patients undergoing cisplatin chemotherapy. PMID:26564230

Minoxidil: an underused vasodilator for resistant or severe hypertension.

PubMed

Sica, Domenic A

2004-05-01

Minoxidil is a direct vasodilator introduced in the early 1970s for the treatment of hypertension. It is capable of reducing blood pressure in most persons with resistant hypertension where therapy has failed with multidrug regimens. Minoxidil's effect can be limited because of an increase in pulse rate and/or sodium (and water) retention. The latter may prove quite debilitating in some patients. Thus, minoxidil is generally administered with both a diuretic and an agent that can keep pulse rate in check, such as a beta blocker or a combined alpha-beta blocker. The prominent tachycardia with minoxidil can aggravate myocardial ischemia and, if long-standing, leads to left ventricular hypertrophy. Minoxidil has a particularly annoying side effect of hypertrichosis that may limit its use, particularly among women. Minoxidil use is infrequently associated with the idiosyncratic onset of a pericardial effusion. If a patient's hypertension is severe enough to warrant minoxidil therapy, a hypertension specialist should probably become involved in the patient's care. The use of this medication should be limited in view of the availability of effective agents with fewer side effects. There is, however, a place for minoxidil in the treatment of resistant hypertension especially in patients with advanced renal disease.

Double external jugular vein and other rare venous variations of the head and neck.

PubMed

Shenoy, Varsha; Saraswathi, Perumal; Raghunath, Gunapriya; Karthik, Jayakumar Sai

2012-12-01

Superficial veins of the head and neck are utilised for central venous cannulation, oral reconstruction and parenteral nutrition in debilitated patients. Clinical and sonological examinations of these veins may provide clues toward underlying cardiac pathology. Hence, although variations in these vessels are common, a sound knowledge of such variations becomes clinically important to surgeons, radiologists and interventional anaesthetists. We report a rare case of a left-sided double external jugular vein where the common facial vein continued as the second external jugular vein, and where there was a communicating channel between the internal jugular vein on the same side and the anterior jugular vein.

Mechanisms of Acupuncture-Electroacupuncture on Persistent Pain

PubMed Central

Zhang, Ruixin; Lao, Lixing; Ren, Ke; Berman, Brian M.

2014-01-01

In the last decade, preclinical investigations of electroacupuncture mechanisms on persistent tissue-injury (inflammatory), nerve-injury (neuropathic), cancer, and visceral pain have increased. These studies show that electroacupuncture activates the nervous system differently in health than in pain conditions, alleviates both sensory and affective inflammatory pain, and inhibits inflammatory and neuropathic pain more effectively at 2–10 Hz than at 100 Hz. Electroacupuncture blocks pain by activating a variety of bioactive chemicals through peripheral, spinal, and supraspinal mechanisms. These include opioids, which desensitize peripheral nociceptors and reduce pro-inflammatory cytokines peripherally and in the spinal cord, and serotonin and norepinephrine, which decrease spinal n-methyl-d-aspartate receptor subunit GluN1 phosphorylation. Additional studies suggest that electroacupuncture, when combined with low dosages of conventional analgesics, provides effective pain management that can forestall the side effects of often-debilitating pharmaceuticals. PMID:24322588

Footsteps on the road to a positive psychology.

PubMed

Gillham, J E; Seligman, M E

1999-07-01

We have argued that psychology as a field has been preoccupied with the negative side of life and has left us with a view of human qualities that is warped and one-sided. Psychology is literally 'half-baked'. We need to bake the other half now. It is time for us to become equally concerned with the qualities and experiences that make life most worthwhile. A balance is needed between work that strives to relieve damage and work that endeavors to build strength. This balance is beautifully exemplified by Jack Rachman's work over the past 40 years. As an astute and compassionate clinician and researcher, Jack developed and evaluated effective treatments for some of the most debilitating anxiety disorders. At the same time, he was impressed by the resiliency of his clients and the courage they exhibited daily. His observations and studies of courage have helped to launch a systematic science of human strengths. They are giant footsteps on the road to a positive psychology.

Comparison of Anxiety Management Training and Self-Control Desensitization.

ERIC Educational Resources Information Center

Deffenbacher, Jerry L.; And Others

1980-01-01

Anxiety management training and self-control desensitization effectively reduced debilitating test anxiety and increased facilitating test anxiety. Follow-up demonstrated maintenance of debilitating test anxiety reduction. Subjects receiving treatment had significantly higher psychology grades. (Author)

A 3-year Randomized Therapeutic Trial of Nitisinone in Alkaptonuria

PubMed Central

Introne, Wendy J.; Perry, Monique B.; Troendle, James; Tsilou, Ekaterini; Kayser, Michael A.; Suwannarat, Pim; O’Brien, Kevin E.; Bryant, Joy; Sachdev, Vandana; Reynolds, James C.; Moylan, Elizabeth; Bernardini, Isa; Gahl, William A.

2011-01-01

Alkaptonuria is a rare, autosomal recessive disorder of tyrosine degradation due to deficiency of the third enzyme in the catabolic pathway. As a result, homogentisic acid (HGA) accumulates and is excreted in gram quantities in the urine, which turns dark upon alkalization. The first symptoms, occurring in early adulthood, involve a painful, progressively debilitating arthritis of the spine and large joints. Cardiac valvular disease and renal and prostate stones occur later. Previously suggested therapies have failed to show benefit, and management remains symptomatic. Nitisinone, a potent inhibitor of the second enzyme in the tyrosine catabolic pathway, is considered a potential therapy; proof-of-principle studies showed 95% reduction in urinary HGA. Based on those findings, a prospective, randomized clinical trial was initiated in 2005 to evaluate 40 patients over a 36-month period. The primary outcome parameter was hip total range of motion with measures of musculoskeletal function serving as secondary parameters. Biochemically, this study consistently demonstrated 95% reduction of HGA in urine and plasma over the course of 3 years. Clinically, primary and secondary parameters did not prove benefit from the medication. Side effects were infrequent. This trial illustrates the remarkable tolerability of nitisinone, its biochemical efficacy, and the need to investigate its use in younger individuals prior to development of debilitating arthritis. PMID:21620748

A 3-year randomized therapeutic trial of nitisinone in alkaptonuria.

PubMed

Introne, Wendy J; Perry, Monique B; Troendle, James; Tsilou, Ekaterini; Kayser, Michael A; Suwannarat, Pim; O'Brien, Kevin E; Bryant, Joy; Sachdev, Vandana; Reynolds, James C; Moylan, Elizabeth; Bernardini, Isa; Gahl, William A

2011-08-01

Alkaptonuria is a rare, autosomal recessive disorder of tyrosine degradation due to deficiency of the third enzyme in the catabolic pathway. As a result, homogentisic acid (HGA) accumulates and is excreted in gram quantities in the urine, which turns dark upon alkalization. The first symptoms, occurring in early adulthood, involve a painful, progressively debilitating arthritis of the spine and large joints. Cardiac valvular disease and renal and prostate stones occur later. Previously suggested therapies have failed to show benefit, and management remains symptomatic. Nitisinone, a potent inhibitor of the second enzyme in the tyrosine catabolic pathway, is considered a potential therapy; proof-of-principle studies showed 95% reduction in urinary HGA. Based on those findings, a prospective, randomized clinical trial was initiated in 2005 to evaluate 40 patients over a 36-month period. The primary outcome parameter was hip total range of motion with measures of musculoskeletal function serving as secondary parameters. Biochemically, this study consistently demonstrated 95% reduction of HGA in urine and plasma over the course of 3 years. Clinically, primary and secondary parameters did not prove benefit from the medication. Side effects were infrequent. This trial illustrates the remarkable tolerability of nitisinone, its biochemical efficacy, and the need to investigate its use in younger individuals prior to development of debilitating arthritis. Published by Elsevier Inc.

Treating individuals with debilitating performance anxiety: An introduction.

PubMed

Powell, Douglas H

2004-08-01

Clinicians often see clients who have debilitating performance anxiety. They suffer from public speaking anxiety, stage fright, test-taking anxiety, and writing block. Their condition is so severe as to threaten to end their academic or professional career. Musicians and athletes also seek help because their anxiety before and during an event causes them to perform at a level well below their demonstrated capabilities. An estimated 2% of the U.S. population is afflicted by debilitating performance anxiety. Effective treatments are now available. This article reviews those behavioral, cognitive, and technological therapies that have shown great promise for treating individuals who have debilitating performance anxiety and introduces this issue of the Journal of Clinical Psychology: In Session devoted to this topic. Copyright 2004 Wiley Periodicals, Inc.

Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities

PubMed Central

Nickoloff, Brian J.; Nestle, Frank O.

2004-01-01

Chronic and excessive inflammation in skin and joints causes significant morbidity in psoriasis patients. As a prevalent T lymphocyte–mediated disorder, psoriasis, as well as the side effects associated with its treatment, affects patients globally. In this review, recent progress is discussed in the areas of genetics, the immunological synapse, the untangling of the cytokine web and signaling pathways, xenotransplantation models, and the growing use of selectively targeted therapies. Since psoriasis is currently incurable, new management strategies are proposed to replace previous serendipitous approaches. Such strategic transition from serendipity to the use of novel selective agents aimed at defined targets in psoriatic lesions is moving rapidly from research benches to the bedsides of patients with this chronic and debilitating disease. PMID:15199399

Opioid-Induced Bowel Dysfunction

PubMed Central

Cheng, Vivian; Lembo, Anthony

2013-01-01

Opioid-induced bowel dysfunction (OIBD) is a potentially debilitating side effect of chronic opioid use. It refers to a collection of primarily gastrointestinal motility disorders induced by opioids, of which opioid-induced constipation (OIC) is the most common. Management of OIBD is difficult, and affected patients will often limit their opioid intake at the expense of experiencing more pain, to reduce the negative impact of OIBD on their quality of life. Effective pharmacologic therapy for OIC is considered an unmet need and several agents have recently been given priority review and approval for OIC. Furthermore, multiple agents currently in development show promise in treating OIC without significant impact on analgesia or precipitation of withdrawal symptoms. The approval and availability of such medications would represent a significant improvement in the management of OIC and OIBD in patients with chronic pain. PMID:23900996

Deep brain stimulation of the anterior internal capsule for the treatment of Tourette syndrome: technical case report.

PubMed

Flaherty, Alice W; Williams, Ziv M; Amirnovin, Ramin; Kasper, Ekkehard; Rauch, Scott L; Cosgrove, G Rees; Eskandar, Emad N

2005-10-01

Medical treatment of Tourette syndrome is often ineffective or is accompanied by debilitating side effects, therefore prompting the need to evaluate surgical therapies. We present the case of a 37-year-old woman with severe Tourette syndrome since the age of 10 years. Her symptoms included frequent vocalizations and severe head and arm jerks that resulted in unilateral blindness. Trials of more than 40 medications and other therapies had failed to relieve the tics. We implanted bilateral electrodes in the anterior limb of the internal capsule, terminating in the vicinity of the nucleus accumbens. At 18-month follow-up, optimal stimulation continued to lower her tic frequency and severity significantly. Our findings suggest that stimulation of the anterior internal capsule may be a safe and effective procedure for the treatment of Tourette syndrome.

AN OBSERVATIONAL STUDY OF SOCIAL CONTROL, MOOD, AND SELF-EFFICACY IN COUPLES DURING TREATMENT FOR HEAD AND NECK CANCER

PubMed Central

BADR, HODA; YEUNG, CHI; LEWIS, MEGAN A.; MILBURY, KATHRIN; REDD, WILLIAM H.

2014-01-01

OBJECTIVE Head and neck cancer (HNC) patients experience debilitating side effects, including abnormally reduced salivation and difficulty swallowing. Intensive self-care protocols are prescribed to control side effects and minimize discomfort, but non-adherence rates are high. Although spouses are in a prime position to encourage adherence, studies have yet to examine how spouse social control (i.e., attempts to influence patient behavior to support adherence) affects HNC patient mood and self-efficacy for engaging in these self-care routines. METHODS One-hundred twenty-five HNC couples where the patient (86% male) was undergoing radiotherapy were recorded in the laboratory as they discussed a cancer-related issue that the patient identified as being a topic of concern. RESULTS Sixty-eight couples discussed side-effects and spouses engaged in social control in 61 of these discussions. Although oral complications and pain were frequently identified by patients as being topics of concern, dental/oral care and pain management were some of the least likely self-care behaviors to be targeted by spouses, who focused primarily on encouraging patients to maintain their weight and hydration. Although spouses engaged in an almost equal number of positive and negative control attempts, only positive control was significantly (p<.05) associated with patient positive mood and self-efficacy. CONCLUSION HNC couples may benefit from programs that emphasize the regular practice of self-care routines to control oral side effects, pain, and nutrition/hydration problems. Likewise, programs that encourage spouses to maximize their use of positive social control may also boost patients’ mood during treatment and empower them to engage in recommended self-care behaviors. PMID:25471820

Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain

PubMed Central

Berta, Temugin; Qadri, Yawar; Tan, Ping-Heng; Ji, Ru-Rong

2018-01-01

Introduction Currently the treatment of chronic pain is inadequate and compromised by debilitating central nervous system side effects. Here we discuss new therapeutic strategies that target dorsal root ganglia (DRGs) in the peripheral nervous system for a better and safer treatment of chronic pain. Areas covered The DRGs contain the cell bodies of primary sensory neurons including nociceptive neurons. After painful injuries, primary sensory neurons demonstrate maladaptive molecular changes in DRG cell bodies and in their axons. These changes result in hypersensitivity and hyperexcitability of sensory neurons (peripheral sensitization) and are crucial for the onset and maintenance of chronic pain. We discuss the following new strategies to target DRGs and primary sensory neurons as a means of alleviating chronic pain and minimizing side effects: inhibition of sensory neuron-expressing ion channels such as TRPA1, TRPV1, and Nav1.7, selective blockade of C- and Aβ-afferent fibers, gene therapy, and implantation of bone marrow stem cells. Expert opinion These peripheral pharmacological treatments, as well as gene and cell therapies, aimed at DRG tissues and primary sensory neurons can offer better and safer treatments for inflammatory, neuropathic, cancer, and other chronic pain states. PMID:28480765

A case series of patients using medicinal marihuana for management of chronic pain under the Canadian Marihuana Medical Access Regulations.

PubMed

Lynch, Mary E; Young, Judee; Clark, Alexander J

2006-11-01

The Canadian Marihuana Medical Access Regulations (MMAR) program allows Health Canada to grant access to marihuana for medical use to those who are suffering from grave and debilitating illnesses. This is a report on a case series of 30 patients followed at a tertiary care pain management center in Nova Scotia who have used medicinal marihuana for 1-5 years under the MMAR program. Patients completed a follow-up questionnaire containing demographic and dosing information, a series of 11-point numerical symptom relief rating scales, a side effect checklist, and a subjective measure of improvement in function. Doses of marihuana ranged from less than 1 to 5g per day via the smoked or oral route of administration. Ninety-three percent of patients reported moderate or greater pain relief. Side effects were reported by 76% of patients, the most common of which were increased appetite and a sense of well-being, weight gain, and slowed thoughts. Limitations of the study include self-selection bias, small size, and lack of a control group. The need for further study using controlled trials is discussed along with an overview of the MMAR program.

Role of Gabapentin in Managing Mucositis Pain in Patients Undergoing Radiation Therapy to the Head and Neck.

PubMed

Milazzo-Kiedaisch, Carol Ann; Itano, Joanne; Dutta, Pinaki R

2016-12-01

Oral mucositis (OM) is a painful and debilitating side effect that affects 80%-100% of patients undergoing radiation therapy for head and neck cancer. This dose-limiting side effect may potentially lead to pain, dehydration, malnutrition, infection, and treatment breaks. Treatment breaks can lead to decreased disease control and suboptimal patient outcomes. No primary prevention exists for OM, and management is focused on pain control. Compelling evidence exists that OM pain has somatic and neuropathic components. This article reviews the existing literature on the use of gabapentin (Neurontin®) as a co-analgesic in treating the neuropathic pain in OM. A literature search was performed using CINAHL® and PubMed with the search terms gabapentin and oral mucositis. The selected articles were briefly screened for relevance, and three were included in this review. No systematic reviews exist on the role of gabapentin for neuropathic pain in radiation-induced OM. Two retrospective studies concluded that gabapentin reduced escalation of opioid doses and unplanned treatment breaks. One retrospective study demonstrated favorable swallowing outcomes. Pain and OM are nursing-sensitive outcomes that can be significantly affected by evidence-based nursing interventions.

Herpes simplex virus vector-mediated gene delivery for the treatment of lower urinary tract pain

PubMed Central

Goins, WF; Goss, JR; Chancellor, MB; de Groat, WC; Glorioso, JC; Yoshimura, N

2009-01-01

Interstitial cystitis (IC)/painful bladder syndrome (PBS) is a painful debilitating chronic visceral pain disorder of unknown etiology that affects an estimated 1 million people in the, United States alone. It is characterized by inflammation of the bladder that results in chronic pelvic pain associated with bladder symptoms of urinary frequency and urgency. Regardless of the etiology, IC/PBS involves either increased and/or abnormal activity in afferent nociceptive sensory neurons. Pain-related symptoms in patients with IC/PBS are often very difficult to treat. Both medical and surgical therapies have had limited clinical utility in this debilitating disease and numerous drug treatments, such as heparin, dimethylsulfoxide and amitriptyline, have proven to be palliative at best, and in some IC/PBS patients provide no relief whatsoever. Although opiate narcotics have been employed to help alleviate IC/PBS pain, this strategy is fraught with problems as systemic narcotic administration causes multiple unwanted side effects including mental status change and constipation. Moreover, chronic systemic narcotic use leads to dependency and need for dose escalation due to tolerance: therefore, new therapies are desperately needed to treat refractory IC/PBS. This has led our group to develop a gene therapy strategy that could potentially alleviate chronic pelvic pain using the herpes simplex virus-directed delivery of analgesic proteins to the bladder. PMID:19242523

Prevention of gastrointestinal side-effects in paediatric oncology: what are the guidelines?

PubMed

Cheng, Karis K F

2017-06-01

Gastrointestinal side-effects, particularly with regard to alimentary tract mucositis and chemotherapy-induced nausea and vomiting (CINV), continue to be frequent and debilitating symptomatic conditions among children and adolescents receiving cytotoxic cancer therapy. Further avenues of progress for mucositis and CINV prevention in paediatric oncology setting are warranted. The current article reviews the major guidelines and literature published in 2016 pertaining to the prevention of mucositis and CINV. Considerable professional organizational efforts have been made to develop consensus-based or evidence-based guidelines that periodically update to define basic standards of mucositis and CINV prevention. There are a few published works in 2016 that may contribute to the emerging evidence on prevention of mucositis and CINV in the paediatric setting for future guideline updates. The concomitant use of 5-HT3 receptor antagonist and dexamethasone are effective to prevent acute and delayed CINV in children who are to receive highly or moderately emetogenic chemotherapy. Optimal control of acute and delayed CINV can prevent anticipatory CINV. Oral care protocols would be beneficial to prevent mucositis in children across all cancer treatment modalities. Cryotherapy or low-level light therapy may be applied to cooperative children undergoing chemotherapy or haematological stem cell transplant conditioning regimens with a high rate of mucositis.

Management of hepatitis C infection in the era of direct-acting antiviral therapy

NASA Astrophysics Data System (ADS)

Zain, L. H.; Sungkar, T.

2018-03-01

Hepatitis C viral infection globally affects millions of people and commonly results in debilitating complications and mortality. Initial mainstay therapy consisted of pegylated interferon α (pegIFNα) with additional ribavirin that showed unsatisfactory cure rate, common side effects and complicated dosing, contributing to high discontinuation rate. Over the last few years, newer antivirals have been extensively studied, that are Direct-Acting Antivirals (DAAs). Specifically targeting viral protein mainly during replication phase, DAAs showed greater cure rate (commonly measured as sustained virologic response), improved safety profile and shorter treatment duration compared to traditional interferon-ribavirin therapy. Current guidelines have also included Interferon-free, often ribavirin-free, DAAs combinations that suggest promising outcomes. The current review highlights development of rapidly growing hepatitis C treatment including DAAs recommendations.

Autogenic feedback training experiment: A preventative method for space motion sickness

NASA Technical Reports Server (NTRS)

Cowings, Patricia S.

1993-01-01

Space motion sickness is a disorder which produces symptoms similar to those of motion sickness on Earth. This syndrome has affected approximately 50 percent of all astronauts and cosmonauts exposed to microgravity in space, but it differs from what is commonly known as motion sickness in a number of critical ways. There is currently no ground-based method for predicting susceptibility to motion sickness in space. Antimotion sickness drugs have had limited success in preventing or counteracting symptoms in space, and frequently caused debilitating side effects. The objectives were: (1) to evaluate the effectiveness of Autogenic-Feedback Training as a countermeasure for space motion sickness; (2) to compare physiological data and in-flight symptom reports to ground-based motion sickness data; and (3) to predict susceptibility to space motion sickness based on pre-flight data of each treatment group crew member.

Using the medical food flavocoxid [corrected] in managing osteoarthritis.

PubMed

Gottlieb, Daniel; Kuritzky, Louis

2011-01-01

Osteoarthritis (OA) is the most common debilitating joint disease worldwide. Clinicians have many therapeutic modalities and prescription medications in their arsenals to treat chronic inflammatory pain. However, as patients age, and develop numerous comorbidities, the most common, and often most effective pharmacologic treatment for OA, nonsteroidal anti-inflammatory drugs (NSAIDs), becomes problematic in that it may exacerbate or even cause cardiovascular, renal, and/or gastrointestinal pathology. This paper reviews the metabolism of arachidonic acid as it relates to the clinical treatment of inflammation, and explores a novel botanical therapy, flavocoxid, that has shown equal efficacy to naproxen in treating pain associated with mild to moderate OA of the knee. Flavocoxid has demonstrated balanced inhibition of the three primary enzymes responsible for processing AA, cyclooxygenases 1 and 2, and 5-lipoxygenase. Researchers have proposed that balanced inhibition of AA metabolism offers the promise of analgesia similar to NSAIDs without the associated cardiovascular, renal, or gastrointestinal side effects.

Patient beliefs and attitudes to taking statins: systematic review of qualitative studies.

PubMed

Ju, Angela; Hanson, Camilla S; Banks, Emily; Korda, Rosemary; Craig, Jonathan C; Usherwood, Tim; MacDonald, Peter; Tong, Allison

2018-06-01

Statins are effective in preventing cardiovascular disease (CVD) events and are recommended for at-risk individuals but estimated adherence rates are low. To describe patients' perspectives, experiences, and attitudes towards taking statins. Systematic review of qualitative studies reporting perspectives of patients on statins. PsycINFO, CINAHL, Embase, MEDLINE, and PhD dissertations from inception to 6 October 2016 were searched for qualitative studies on adult patients' perspectives on statins. All text and participant quotations were extracted from each article and analysed by thematic synthesis. Thirty-two studies involving 888 participants aged 22-93 years across eight countries were included. Seven themes were identified: confidence in prevention (trust in efficacy, minimising long-term catastrophic CVD, taking control, easing anxiety about high cholesterol); routinising into daily life; questioning utility (imperceptible benefits, uncertainties about pharmacological mechanisms); medical distrust (scepticism about overprescribing, pressure to start therapy); threatening health (competing priorities and risks, debilitating side effects, toxicity to body); signifying sickness (fear of perpetual dependence, losing the battle); and financial strain. An expectation that statins could prevent CVD and being able to integrate the statin regimen in daily life facilitated acceptance of statins among patients. However, avoiding the 'sick' identity and prolonged dependence on medications, uncertainties about the pharmacological mechanisms, risks to health, side effects, costs, and scepticism about clinicians' motives for prescribing statins were barriers to uptake. Shared decision making that addresses the risks, reasons for prescribing, patient priorities, and implementing strategies to minimise lifestyle intrusion and manage side effects may improve patient satisfaction and continuation of statins. © British Journal of General Practice 2018.

The Effect of Metformin and Cinnamon on Serum Anti-Mullerian Hormone in Women Having PCOS: A Double-Blind, Randomized, Controlled Trial.

PubMed

Wiweko, Budi; Susanto, Cynthia A

2017-01-01

Polycystic ovary syndrome (PCOS) is known to be associated with insulin resistance and anti-Mullerian hormone (AMH), leading to the use of insulin-sensitizing agents (ISAs) to manage PCOS. Metformin is the most widely used ISA to treat irregular menstruation; however, the gastrointestinal side effects are quite debilitating. The development of herbal medicines such as bioactive fraction DLBS3233 offers a possibly effective treatment with minimal side effects. To determine the effect of metformin and DLBS3233 on serum AMH level. This study was a double-blind, randomized, controlled trial conducted between March 2013 and June 2015 at Yasmin Clinic, RSCM Kencana, Jakarta and Hasan Sadikin Hospital, Bandung. The patients with PCOS were diagnosed using the Rotterdam criteria. All participants received daily treatment consisting of 1500 mg metformin divided into two doses or 100 mg DLBS3233 for 6 months. An evaluation of serum AMH level was conducted before and after the completion of therapy. Twenty patients received metformin, whereas 18 patients received DLBS3233. The levels of AMH prior to the intervention were 9.30 ± 5.06 ng/mL and 11.27 ± 6.47 ng/mL. After 6 months of therapy, we found that the decrease in AMH level was higher in the metformin group compared to the DLBS3233 group (ΔAMH = 1.83 ng/mL, P = 0.003 and ΔAMH = 1.15 ng/mL, P = 0.077, respectively). However, more side effects were observed in the metformin group compared to the DLBS3233 group ( P = 0.01). A total of seven patients (18.42%) were confirmed as pregnant during the study. There was a significant decrease in the serum AMH level after administration of either metformin or DLBS3233.

Low level laser therapy in the treatment of oral mucositis in cancer patients: systematic review of literature

NASA Astrophysics Data System (ADS)

El-Sabbagh, Rula Fawzi; Selting, Wayne J.

2016-03-01

Oral mucositis is a debilitating and dose limiting side effect of oncotherapy in cancer patients. Low Level Laser Therapy (LLLT) is a promising new intervention for the treatment of oral mucositis. Aims and objectives: 1. Perform a systematic review of available literature on the therapeutic effect of LLLT on established oral mucositis. 2. Formulate recommendations for future studies based on results of review. Methods: Electronic search oflow level laser therapy in the treatment of oral mucositis was conducted and eligible studies reviewed. Results: Four studies met the inclusion criteria and were analyzed. A total of 109 patients were included, 59 of which received LLLT as a therapeutic measure. An overall success rate of 81.4% success rate was reported in regard to OM. Conclusion: The review demonstrated the positive therapeutic effect of LLLT on oral mucositis. However, the need for future studies with standardized reporting of parameters and methods is needed to increase the level of evidence of this intervention.

The Effect of Intravenous Vitamin C on Cancer- and Chemotherapy-Related Fatigue and Quality of Life

PubMed Central

Carr, Anitra C.; Vissers, Margreet C. M.; Cook, John S.

2014-01-01

Cancer patients commonly experience a number of symptoms of disease progression and the side-effects of radiation therapy and adjuvant chemotherapy, which adversely impact on their quality of life (QOL). Fatigue is one of the most common and debilitating symptom reported by cancer patients and can affect QOL more than pain. Several recent studies have indicated that intravenous (IV) vitamin C alleviates a number of cancer- and chemotherapy-related symptoms, such as fatigue, insomnia, loss of appetite, nausea, and pain. Improvements in physical, role, cognitive, emotional, and social functioning, as well as an improvement in overall health, were also observed. In this mini review, we briefly cover the methods commonly used to assess health-related QOL in cancer patients, and describe the few recent studies examining the effects of IV vitamin C on cancer- and chemotherapy-related QOL. We discuss potential mechanisms that might explain an improvement in QOL and also considerations for future studies. PMID:25360419

Hypoxia and hypoxia inducible factor-1α are required for normal endometrial repair during menstruation.

PubMed

Maybin, Jacqueline A; Murray, Alison A; Saunders, Philippa T K; Hirani, Nikhil; Carmeliet, Peter; Critchley, Hilary O D

2018-01-23

Heavy menstrual bleeding (HMB) is common and debilitating, and often requires surgery due to hormonal side effects from medical therapies. Here we show that transient, physiological hypoxia occurs in the menstrual endometrium to stabilise hypoxia inducible factor 1 (HIF-1) and drive repair of the denuded surface. We report that women with HMB have decreased endometrial HIF-1α during menstruation and prolonged menstrual bleeding. In a mouse model of simulated menses, physiological endometrial hypoxia occurs during bleeding. Maintenance of mice under hyperoxia during menses decreases HIF-1α induction and delays endometrial repair. The same effects are observed upon genetic or pharmacological reduction of endometrial HIF-1α. Conversely, artificial induction of hypoxia by pharmacological stabilisation of HIF-1α rescues the delayed endometrial repair in hypoxia-deficient mice. These data reveal a role for HIF-1 in the endometrium and suggest its pharmacological stabilisation during menses offers an effective, non-hormonal treatment for women with HMB.

Psoriasis treatment considerations in military patients: unique patients, unique drugs.

PubMed

Evans, Thomas; Davidson, Nathan; Logemann, Nicholas

2016-12-01

Psoriasis is a common dermatologic problem with a chronic and sometimes debilitating course. Psoriasis can impair a service member's ability to perform job-related activities and should certainly be treated; however, use of immunosuppressive treatments can prevent deployment to strategic locations around the world for numerous reasons, such as the need for laboratory monitoring, minimal access to climate-controlled storage, and potential increased risk of exposure to virulent pathogens while on these medications. Similar obstacles can exist for nonmilitary patients who are placed in austere conditions or participate in worldwide travel. Although treatment efficacy, cost, and side-effect profiles are always paramount considerations in deciding on treatment regimens with patients, herein we focus our discussion on a consideration that might be easily overlooked when treating patients in modern society, that being the "logistics" of treatment.

Are Medications Involved in Vision and intracranial Pressure Changes Seen in Spaceflight?

NASA Technical Reports Server (NTRS)

Wotring, V. E.

2016-01-01

Some crewmembers have experienced changes in their vision after long-duration spaceflight on the ISS. These impairments include visual performance decrements, development of cotton-wool spots or choroidal folds, optic-disc edema, optic nerve sheath distention, and/or posterior globe flattening with varying degrees of severity and permanence. These changes are now used to define the visual impairment/intracranial pressure (VIIP) syndrome. The reasons for these potentially debilitating medical issues are currently unknown. The potential role of administered medications has not yet been examined, but it is known that many medications can have side effects that are similar to VIIP symptoms. Some medications raise blood pressure, which can affect intracranial pressure. Many medications that act in the central nervous system can affect intracranial pressures and/or vision. About 40% of the medications in the ISS kit are known to cause side effects involving changes in blood pressure, intracranial pressure and/or vision. For this reason, we proposed an investigation of the potential relationship between ISS medications and their risk of causing or exacerbating VIIP-like symptoms. The purpose of this study was to use medication usage records for affected and unaffected crew to determine if use of particular medications seemed to correlate with VIIP occurrence or severity.

Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments

PubMed Central

McQuade, Rachel M.; Stojanovska, Vanesa; Abalo, Raquel; Bornstein, Joel C.; Nurgali, Kulmira

2016-01-01

Gastrointestinal (GI) side-effects of chemotherapy are a debilitating and often overlooked clinical hurdle in cancer management. Chemotherapy-induced constipation (CIC) and Diarrhea (CID) present a constant challenge in the efficient and tolerable treatment of cancer and are amongst the primary contributors to dose reductions, delays and cessation of treatment. Although prevalence of CIC is hard to estimate, it is believed to affect approximately 16% of cancer patients, whilst incidence of CID has been estimated to be as high as 80%. Despite this, the underlying mechanisms of both CID and CIC remain unclear, but are believed to result from a combination of intersecting mechanisms including inflammation, secretory dysfunctions, GI dysmotility and alterations in GI innervation. Current treatments for CIC and CID aim to reduce the severity of symptoms rather than combating the pathophysiological mechanisms of dysfunction, and often result in worsening of already chronic GI symptoms or trigger the onset of a plethora of other side-effects including respiratory depression, uneven heartbeat, seizures, and neurotoxicity. Emerging treatments including those targeting the enteric nervous system present promising avenues to alleviate CID and CIC. Identification of potential targets for novel therapies to alleviate chemotherapy-induced toxicity is essential to improve clinical outcomes and quality of life amongst cancer sufferers. PMID:27857691

Development and Usability Testing of a Web-based Self-management Intervention for Oral Cancer Survivors and their Family Caregivers

PubMed Central

Badr, Hoda; Lipnick, Daniella; Diefenbach, Michael A; Posner, Marshall; Kotz, Tamar; Miles, Brett; Genden, Eric

2016-01-01

Oral cancer (OC) survivors experience debilitating side effects that affect their quality of life (QOL) and that of their caregivers. This study aimed to develop and evaluate a dyadic, web-based intervention to improve survivor self-management and survivor/caregiver QOL. A qualitative needs assessment (semi-structured interviews) with 13 OC survivors and 12 caregivers was conducted to discern information and support needs as well as preferences regarding website features and tools. Results using Grounded Theory analysis showed that OC survivors and caregivers: 1) want and need practical advice about managing side effects; 2) want to reach out to other survivors/caregivers for information and support; and, 3) have both overlapping and unique needs and preferences regarding website features. Usability testing (N=6 survivors; 5 caregivers) uncovered problems with the intuitiveness, navigation, and design of the website that were subsequently addressed. Users rated the website favorably on the dimensions of attractiveness, controllability, efficiency, intuitiveness, and learnability, and gave it a total usability score of 80/100. Overall, this study demonstrates that OC survivors and caregivers are interested in using an online program to improve QOL, and that providing tailored website content and features based on the person’s role as survivor or caregiver is important in this population. PMID:26507369

Girls Can Play Ball: Stereotype Threat Reduces Variability in a Motor Skill

PubMed Central

Huber, Meghan E.; Brown, Adam J.; Sternad, Dagmar

2016-01-01

The majority of research on stereotype threat shows what is expected: threat debilitates performance. However, facilitation is also possible, although seldom reported. This study investigated how stereotype threat influences novice females when performing the sensorimotor task of bouncing a ball to target. We tested the predictions of two prevailing accounts for debilitation and facilitation due to ST effects: working memory and mere effort. Experimental results showed that variability in performance decreased more in stigmatized females than in control females, consistent with the prediction of the mere effort account, but inconsistent with the working memory account. These findings suggest that stereotype threat effects may be predicated upon the correctness of the dominant motor behavior rather than on a novice-expert distinction or task difficulty. Further, a comprehensive understanding should incorporate the fact that stereotype threat can facilitate, as well as debilitate, performance. PMID:27249638

Girls can play ball: Stereotype threat reduces variability in a motor skill.

PubMed

Huber, Meghan E; Brown, Adam J; Sternad, Dagmar

2016-09-01

The majority of research on stereotype threat shows what is expected: threat debilitates performance. However, facilitation is also possible, although seldom reported. This study investigated how stereotype threat influences novice females when performing the sensorimotor task of bouncing a ball to a target. We tested the predictions of two prevailing accounts for debilitation and facilitation due to sterotype threat effects: working memory and mere effort. Experimental results showed that variability in performance decreased more in stigmatized females than in control females, consistent with the prediction of the mere effort account, but inconsistent with the working memory account. These findings suggest that stereotype threat effects may be predicated upon the correctness of the dominant motor behavior, rather than on a novice-expert distinction or task difficulty. Further, a comprehensive understanding should incorporate the fact that stereotype threat can facilitate, as well as debilitate, performance. Copyright © 2016 Elsevier B.V. All rights reserved.

Nutraceuticals and chemotherapy induced peripheral neuropathy (CIPN): a systematic review.

PubMed

Schloss, Janet M; Colosimo, Maree; Airey, Caroline; Masci, Paul P; Linnane, Anthony W; Vitetta, Luis

2013-12-01

Chemotherapy induced peripheral neuropathy [CIPN] is a common significant and debilitating side effect resulting from the administration of neurotoxic chemotherapeutic agents. These pharmaco-chemotherapeutics can include taxanes, vinca alkaloids and others. Moderate to severe CIPN significantly decreases the quality of life and physical abilities of cancer patients and current pharmacotherapy for CIPN e.g. Amifostine and antidepressants have had limited efficacy and may themselves induce adverse side effects. To determine the potential use of nutraceuticals i.e. vitamin E, acetyl-L-carnitine, glutamine, glutathione, vitamin B6, omega-3 fatty acids, magnesium, calcium, alpha lipoic acid and n-acetyl cysteine as adjuvants in cancer treatments a systematic literature review was conducted. Revised clinical studies comprised of randomized clinical trials that investigated the anti-CIPN effect of nutraceuticals as the adjuvant intervention in patients administered chemotherapy. Twenty-four studies were assessed on methodological quality and limitations identified. Studies were mixed in their recommendations for nutraceuticals. Currently no agent has shown solid beneficial evidence to be recommended for the treatment or prophylaxis of CIPN. The standard of care for CIPN includes dose reduction and/or discontinuation of chemotherapy treatment. The management of CIPN remains an important challenge and future studies are warranted before recommendations for the use of supplements can be made. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Ketamine Does Not Produce Relief of Neuropathic Pain in Mice Lacking the β-Common Receptor (CD131)

PubMed Central

Swartjes, Maarten; Niesters, Marieke; Heij, Lara; Dunne, Ann; Aarts, Leon; Hand, Carla Cerami; Kim, Hyung-Suk; Brines, Michael; Cerami, Anthony; Dahan, Albert

2013-01-01

Neuropathic pain (NP) is a debilitating condition associated with traumatic, metabolic, autoimmune and neurological etiologies. Although the triggers for NP are diverse, there are common underlying pathways, including activation of immune cells in the spinal cord and up-regulation of the N-methyl-D-aspartate receptor (NMDAR). Ketamine, a well-known NDMAR antagonist, reduces neuropathic pain in a sustained manner. Recent study has shown that the novel 11-amino acid peptide erythropoietin derivative ARA290 produces a similar, long-lasting relief of NP. Here, we show that both drugs also have similar effects on the expression of mRNA of the NMDAR, as well as that of microglia, astrocytes and chemokine (C-C motif) ligand 2, all-important contributors to the development of NP. Although the effects of ketamine and ARA 290 on NP and its molecular mediators suggest a common mechanism of action, ARA 290 has no affinity for the NMDAR and acts specifically via the innate repair receptor (IRR) involved in tissue protection. We speculated therefore, that the IRR might be critically involved in the action of ketamine on neuropathic pain. To evaluate this, we studied the effects of ketamine and ARA 290 on acute pain, side effects, and allodynia following a spared nerve injury model in mice lacking the β-common receptor (βcR), a structural component of the IRR. Ketamine (50 mg/kg) and ARA 290 (30 µg/kg) produced divergent effects on acute pain: ketamine produced profound antinociception accompanied with psychomotor side effects, but ARA290 did not, in both normal and knock out mice. In contrast, while both drugs were antiallodynic in WT mice, they had no effect on NP in mice lacking the βcR. Together, these results show that an intact IRR is required for the effective treatment of NP with either ketamine or ARA 290, but is not involved in ketamine’s analgesic and side effects. PMID:23936499

Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues

PubMed Central

Lai, Samuel K.; Wang, Ying-Ying; Hanes, Justin

2009-01-01

Mucus is a viscoelastic and adhesive gel that protects the lung airways, gastrointestinal (GI) tract, vagina, eye and other mucosal surfaces. Most foreign particulates, including conventional particle-based drug delivery systems, are efficiently trapped in human mucus layers by steric obstruction and/or adhesion. Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on anatomical location, thereby strongly limiting the duration of sustained drug delivery locally. A number of debilitating diseases could be treated more effectively and with fewer side effects if drugs and genes could be more efficiently delivered to the underlying mucosal tissues in a controlled manner. This review first describes the tenacious mucus barrier properties that have precluded the efficient penetration of therapeutic particles. It then reviews the design and development of new mucus-penetrating particles that may avoid rapid mucus clearance mechanisms, and thereby provide targeted or sustained drug delivery for localized therapies in mucosal tissues. PMID:19133304

Cutaneous ulcers associated with hydroxyurea therapy.

PubMed

Quattrone, Filippo; Dini, Valentina; Barbanera, Sabrina; Zerbinati, Nicola; Romanelli, Marco

2013-11-01

Hydroxyurea is an antitumoral drug mainly used in the treatment of Philadelphia chromosome-negative myeloproliferative syndromes and sickle-cell disease. Ulcers represent a rare but severe long-term adverse effect of hydroxyurea therapy. Hydroxyurea-induced ulcers are often multiple and bilateral, typically developing in the perimalleolar region, although any cutaneous district is potentially affected. They generally look small, well-defined, shallow with an adherent, yellow, fibrinous necrotic base. A constant finding is also an extremely intense, treatment-resistant pain accompanying these ulcerations. Withdrawal of the drug generally leads to spontaneous healing of these lesions. Care providers tend to show insufficient awareness of this highly debilitating cutaneous side effect, and late or missed diagnoses are frequent. Instead, regular dermatologic screening should be performed on hydroxyurea-treated patients. This article will present a comprehensive review of indexed case reports and clinical studies, followed by a discussion about treatment options aiming at increasing knowledge about this specific topic. Copyright © 2013 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Current Status of Immunomodulatory and Cellular Therapies in Preclinical and Clinical Islet Transplantation

PubMed Central

Chhabra, Preeti; Brayman, Kenneth L.

2011-01-01

Clinical islet transplantation is a β-cell replacement strategy that represents a possible definitive intervention for patients with type 1 diabetes, offering substantial benefits in terms of lowering daily insulin requirements and reducing incidences of debilitating hypoglycemic episodes and unawareness. Despite impressive advances in this field, a limiting supply of islets, inadequate means for preventing islet rejection, and the deleterious diabetogenic and nephrotoxic side effects associated with chronic immunosuppressive therapy preclude its wide-spread applicability. Islet transplantation however allows a window of opportunity for attempting various therapeutic manipulations of islets prior to transplantation aimed at achieving superior transplant outcomes. In this paper, we will focus on the current status of various immunosuppressive and cellular therapies that promote graft function and survival in preclinical and clinical islet transplantation with special emphasis on the tolerance-inducing capacity of regulatory T cells as well as the β-cells regenerative capacity of stem cells. PMID:22046502

Pathogenesis of Endometriosis: Roles of Retinoids and Inflammatory Pathways

PubMed Central

Taylor, Robert N.; Kane, Maureen A.; Sidell, Neil

2016-01-01

Endometriosis is a nonmalignant, but potentially metastatic, gynecological condition manifested by the extrauterine growth of inflammatory endometrial implants. Ten percent of reproductive-age women are affected and commonly suffer pelvic pain and/ or infertility. The theories of endometriosis histogenesis remain controversial, but retrograde menstruation and metaplasia each infer mechanisms that explain the immune cell responses observed around the ectopic lesions. Recent findings from our laboratories and others suggest that retinoic acid metabolism and action are fundamentally flawed in endometriotic tissues and even generically in women with endometriosis. The focus of our ongoing research is to develop medical therapies as adjuvants or alternatives to the surgical excision of these lesions. On the basis of concepts put forward in this review, we predict that the pharmacological actions and anticipated low side-effect profiles of retinoid supplementation might provide a new treatment option for the long-term management of this chronic and debilitating gynecological disease. PMID:26132929

Mother's milk and the muffin man: grassroots innovations in medical marijuana delivery systems.

PubMed

Chapkis, Wendy; Webb, Richard J

2005-01-01

In the ongoing debates over medical marijuana, opponents often conflate the alleged risks of cannabis therapeutics with the acknowledged harms associated with smoking. Although smoking is the most widely used method of administering marijuana, it is not the only available means. This paper provides an account of the production, distribution, and administration of non-smokable cannabis products by members of a California health care collective, the Wo/Men's Alliance for Medical Marijuana. WAMM has developed a variety of alternative methods of administering cannabis orally and externally that challenge the rhetorical equivalence between smoking as a delivery method and botanical marijuana as a medicine. Their experience with low-cost and low-tech production techniques has enabled even the poor and uninsured among them to manage the debilitating symptoms of their illnesses and the side-effects of their often onerous courses of treatment, without smoking. The organization provides an informative example of.

Hypobaric spinal anesthesia in the operative management of orthopedic emergencies in geriatric patients.

PubMed

Sidi, A; Pollak, D; Floman, Y; Davidson, J T

1984-07-01

Hypobaric spinal anesthesia was administered to 40 patients undergoing lower limb surgery. Twenty-nine of the patients were debilitated geriatric patients who presented with orthopedic emergencies, in most cases a fractured hip. Hypobaric spinal anesthesia was found to be a simple and safe procedure that provided adequate analgesia. Due to its inherent nature, hypobaric spinal anesthesia does not necessitate positioning of the patient on the injured, painful side (unlike hyperbaric spinal or epidural anesthesia) and, therefore, facilitates a smooth and painless transfer of the patient to the operating table. Complications encountered were similar to those following hyperbaric anesthesia.

Effect of stapedotomy on pre-operative tinnitus and its psychosomatic burden.

PubMed

Bast, Florian; Mazurek, Birgit; Schrom, Thomas

2013-12-01

According to the literature, between 40 and 90% of otosclerosis patients suffering from hearing loss also suffer from tinnitus on the affected side. For a lot of these patients tinnitus represents a handicap that is just as debilitating as the hearing loss itself. The main goal of the surgical treatment of otosclerosis is a significant improvement in hearing loss, but frequent reports of reduced tinnitus after surgery suggest that this can be a positive side effect. All patients who underwent stapedotomy were initially included in the study. Retrospectively, the tinnitus questionnaire as compiled by Goebel and Hiller was sent to the patients, and 34 patients (37 ears) replied. The pre- and postoperative cases of tinnitus were divided into compensated and non-compensated tinnitus. In addition the following tinnitus-related factors were evaluated: emotional, cognitive and mental burden; intrusiveness of the tinnitus; hearing problems; somatic ailments; and sleep disturbances. Over 80% of the patients surveyed suffered from tinnitus pre-operation. The tinnitus disappeared or improved in over 60% of the cases after stapedotomy. In addition, the related factors surveyed also improved appreciably post surgery and reached a significant level in patients with compensated tinnitus. Besides a significant improvement in hearing loss the intensity and the psychosomatic burden of a pre-operative tinnitus can be reduced by stapedotomy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Strontium 89 in the treatment of pain due to diffuse osseous metastases: a university hospital experience.

PubMed Central

Ashayeri, Ebrahim; Omogbehin, Adedamola; Sridhar, Rajagopalan; Shankar, Ravi A.

2002-01-01

More than two-thirds of the patients with osseous metastases experience debilitating bone pain, requiring some form of pain relief. Analgesics are limited in their efficacy. Palliative application of hemi-body external beam radiation therapy in the treatment of multiple osseous metastases also is limited due to toxicity associated with large treatment ports. Intravenous injections of bone seeking radioisotopes are effective in the palliation of pain with fewer side effects. Forty-one patients with multiple osseous metastases due to prostate and breast cancer were treated with strontium chloride 89 (89Sr) at the department of radiation oncology, in a university hospital. A retrospective analysis of these patients indicated that all subjects had severe pain that diminished their quality of life. Most of these patients had multiple co-morbid factors. Many were on opioids leading to adverse effects such as nausea, constipation, and drowsiness that required additional medication. Objective findings and evaluation of the responses were not always available for all patients. Following treatmentwith 89Sr, over two-thirds of the patients responded favorably and required lower doses of opioids. PMID:12152927

Astroglial networks and implications for therapeutic neuromodulation of epilepsy.

PubMed

Witcher, Mark R; Ellis, Thomas L

2012-01-01

Epilepsy is a common chronic neurologic disorder affecting approximately 1% of the world population. More than one-third of all epilepsy patients have incompletely controlled seizures or debilitating medication side effects in spite of optimal medical management. Medically refractory epilepsy is associated with excess injury and mortality, psychosocial dysfunction, and significant cognitive impairment. Effective treatment options for these patients can be limited. The cellular mechanisms underlying seizure activity are incompletely understood, though we here describe multiple lines of evidence supporting the likely contribution of astroglia to epilepsy, with focus on individual astrocytes and their network functions. Of the emerging therapeutic modalities for epilepsy, one of the most intriguing is the field of neuromodulation. Neuromodulatory treatment, which consists of administering electrical pulses to neural tissue to modulate its activity leading to a beneficial effect, may be an option for these patients. Current modalities consist of vagal nerve stimulation, open and closed-loop stimulation, and transcranial magnetic stimulation. Due to their unique properties, we here present astrocytes as likely important targets for the developing field of neuromodulation in the treatment of epilepsy.

Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism Following Chronic Haloperidol Administration.

PubMed

McClay, Joseph L; Vunck, Sarah A; Batman, Angela M; Crowley, James J; Vann, Robert E; Beardsley, Patrick M; van den Oord, Edwin J

2015-09-01

Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p < 0.05 level. Top compounds were robust to analytical method, also being identified via partial least squares discriminant analysis. Four compounds (sphinganine, N-acetylornithine, leucine and adenosine diphosphate) survived correction for multiple testing in a non-parametric analysis using false discovery rate threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05) revealed significant findings for sphingolipid metabolism (p = 0.015) and protein biosynthesis (p = 0.024). Altered sphingolipid metabolism is suggestive of disruptions to myelin. This interpretation is supported by our observation of elevated N-acetyl-aspartyl-glutamate in the haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects.

Neurochemical metabolomics reveals disruption to sphingolipid metabolism following chronic haloperidol administration

PubMed Central

McClay, Joseph L.; Vunck, Sarah A.; Batman, Angela M.; Crowley, James J.; Vann, Robert E.; Beardsley, Patrick M.; van den Oord, Edwin J.

2015-01-01

Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p < 0.05 level. Top compounds were robust to analytical method, also being identified via partial least squares discriminant analysis. Four compounds (sphinganine, N-acetylornithine, leucine and adenosine diphosphate) survived correction for multiple testing in a non-parametric analysis using false discovery rate threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05) revealed significant findings for sphingolipid metabolism (p = 0.02) and protein biosynthesis (p = 0.03). Altered sphingolipid metabolism is suggestive of disruptions to myelin. This interpretation is supported by our observation of elevated N-acetylaspartylglutamate in the haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects. PMID:25850894

Now You Feel both: Galvanic Vestibular Stimulation Induces Lasting Improvements in the Rehabilitation of Chronic Tactile Extinction

PubMed Central

Schmidt, Lena; Utz, Kathrin S.; Depper, Lena; Adams, Michaela; Schaadt, Anna-Katharina; Reinhart, Stefan; Kerkhoff, Georg

2013-01-01

Tactile extinction is frequent, debilitating, and often persistent after brain damage. Currently, there is no treatment available for this disorder. In two previous case studies we showed an influence of galvanic vestibular stimulation (GVS) on tactile extinction. Here, we evaluated in further patients the immediate and lasting effects of GVS on tactile extinction. GVS is known to induce polarity-specific changes in cerebral excitability in the vestibular cortices and adjacent cortical areas. Tactile extinction was examined with the Quality Extinction Test (QET) where subjects have to discriminate six different tactile fabrics in bilateral, double simultaneous stimulations on their dorsum of hands with identical or different tactile fabrics. Twelve patients with stable left-sided tactile extinction after unilateral right-hemisphere lesions were divided into two groups. The GVS group (N = 6) performed the QET under six different experimental conditions (two Baselines, Sham-GVS, left-cathodal/right-anodal GVS, right-cathodal/left-anodal GVS, and a Follow-up test). The second group of patients with left-sided extinction (N = 6) performed the QET six times repetitively, but without receiving GVS (control group). Both right-cathodal/left-anodal as well as left-cathodal/right-anodal GVS (mean: 0.7 mA) improved tactile identification of identical and different stimuli in the experimental group. These results show a generic effect of GVS on tactile extinction, but not in a polarity-specific way. These observed effects persisted at follow-up. Sham-GVS had no significant effect on extinction. In the control group, no significant improvements were seen in the QET after the six measurements of the QET, thus ruling out test repetition effects. In conclusion, GVS improved bodily awareness permanently for the contralesional body side in patients with tactile extinction and thus offers a novel treatment option for these patients. PMID:23519604

Hematology and serum biochemistry in debilitated, free-ranging raccoon dogs (Nyctereutes procyonoides) infested with sarcoptic mange.

PubMed

Kido, Nobuhide; Kamegaya, Chihiro; Omiya, Tomoko; Wada, Yuko; Takahashi, Maya; Yamamoto, Yasuhiko

2011-12-01

Frequent outbreaks of Sarcoptes scabiei infestation in raccoon dogs (Nyctereutes procyonoides) have been reported in Japan. Although many raccoon dogs are brought to Kanazawa Zoological Garden (Yokohama, Kanagawa, Japan) because of S. scabiei infestation and debilitation, some of them die of asthenia. The clinical status of severely debilitated raccoon dogs must be determined to save their lives. In this study, we compared hematological and serum biochemical values between severely debilitated and nondebilitated raccoon dogs infested with S. scabiei. The total protein, albumin, glucose, and calcium values of debilitated raccoon dogs were significantly lower than those of nondebilitated raccoon dogs. On the other hand, debilitated raccoon dogs had significantly higher aspartate aminotransferase, total bilirubin, blood urea nitrogen, sodium, chloride, and phosphorus values than did nondebilitated raccoon dogs. The increase in the blood urea nitrogen value was particularly dramatic. The present study revealed that debilitated raccoon dogs infested with S. scabiei exhibited abnormal hematological values compared with nondebilitated raccoon dogs infested with S. scabiei. Clinically, the raccoon dogs developed malnutrition and sepsis if the mange infestation was untreated. Moreover, dehydration associated with appetite loss may have resulted in insufficient renal perfusion. These findings suggest that chronic S. scabiei infestations debilitated the raccoon dogs and resulted in physiological changes that were detected with hematological and serum biochemical tests. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Establishment of reference values for various coagulation tests in healthy Florida manatees (Trichechus manatus latirostris) and evaluation of coagulation in debilitated manatees during rehabilitation.

PubMed

Gerlach, Trevor J; Bandt, Carsten; Conner, Bobbi; Ball, Ray L

2015-11-01

To establish reference ranges for coagulation parameters in healthy Florida manatees (Trichechus manatus latirostris) and compare results with those for debilitated manatees undergoing treatment at a rehabilitation facility. Prospective study. 29 healthy manatees and 45 debilitated manatees with various diseases. Manatees considered healthy on the basis of results of physical examination, CBC, and serum biochemical analysis underwent coagulation testing including measurement of prothrombin time, partial thromboplastin time, D-dimer concentration, platelet count, and fibrinogen concentration to establish reference ranges. For comparison, a group of manatees undergoing rehabilitation was also tested, and the results were compared. Thromboelastography was also performed on some animals. Values for D-dimer concentration were significantly higher in debilitated versus healthy animals. There was no significant difference for prothrombin time, partial thromboplastin time, platelet count, or fibrinogen concentration between groups. Thromboelastography was performed on 8 healthy animals. Reference ranges were established for various tests of coagulation that may assist clinicians during the initial evaluation and rehabilitation of Florida manatees. Future research to evaluate the effect of specific disease processes on the coagulation cascade is recommended.

Evolving Concepts in Posterior Subthalamic Area Deep Brain Stimulation for Treatment of Tremor: Surgical Neuroanatomy and Practical Considerations.

PubMed

Ramirez-Zamora, Adolfo; Smith, Heather; Kumar, Vignessh; Prusik, Julia; Phookan, Sujoy; Pilitsis, Julie G

2016-01-01

Although thalamic deep brain stimulation (DBS) has been established as an effective therapy for refractory tremor in Parkinson's disease and essential tremor, reports investigating the efficacy of posterior subthalamic area (PSA) DBS for severe, debilitating tremors continue to emerge. However, questions regarding the optimal anatomical target, surgical approach, programming paradigms and effectiveness compared to other targets remain. In this report, we aimed to review the current literature to assess different stereotactic techniques, anatomical considerations, adverse effects and stimulation settings in PSA DBS. A comprehensive literature review was performed searching for articles discussing tremors and PSA stimulation. We performed a quantitative analysis comparing different DBS tremor targets. Tremor improvement is consistently documented in most reports with an average reduction in tremor of 79% depending on the specific tremor syndrome. Tremor benefit in patients with multiple sclerosis (MS) tremor was significantly higher than for other stimulation targets. Transient paresthesias, imbalance, dizziness and dysarthria are the most common side effects with PSA DBS. PSA DBS is an effective and safe treatment for tremor control and should be considered in patients with refractory tremors with associated cerebellar or dystonic features, proximal tremors and MS tremor. © 2016 S. Karger AG, Basel.

Resolution of long standing tinnitus following radiofrequency ablation of C2-C3 medial branches--a case report.

PubMed

Gritsenko, Karina; Caldwell, William; Shaparin, Naum; Vydyanathan, Amaresh; Kosharskyy, Boleslav

2014-01-01

Tinnitus is described as an auditory phantom perception analogous to central neuropathic pain. Despite the high prevalence of this debilitating symptom, no intervention is recognized that reliably eliminates tinnitus symptoms; a cause has yet to be determined. A 65-year-old healthy man presented with a 3 year history of left-sided tinnitus. Full workup performed by the primary care physician including blood tests for electrolyte imbalance, consultations by 2 independent otholaryngologists, and imaging did not reveal abnormalities to provide etiology of the tinnitus. No other complaints were noted except for occasional minimal left sided neck pain. Cervical spine x-ray showed degenerative changes with facet hypertrophy more pronounced on the left side. Subsequently, the patient underwent diagnostic left-sided C2-C3 medial branch block, resulting in complete resolution of tinnitus for more than 6 hours. After successful radiofrequency ablation of left C2-C3 medial branches, the patient became asymptomatic. At one year follow-up, he continued to be symptom free. Sparce studies have shown interaction between the somatosensory and auditory system at dorsal cochlear nucleus (DCN), inferior colliculus, and parietal association areas. Upper cervical nerve (C2) electrical stimulation evokes potentials in the DCN, eliciting strong patterns of inhibition and weak excitation of the DCN principal cells. New evidence demonstrated successful transcutaneous electrical nerve stimulation (TENS) of upper cervical nerve (C2) for treatment of somatic tinnitus in 240 patients. This case indicates that C2-C3 facet arthropathy may cause tinnitus and radiofrequency ablation of C2-C3 medial branches can provide an effective approach not previously considered.

Dairy milk fat augments paclitaxel therapy to suppress tumour metastasis in mice, and protects against the side-effects of chemotherapy.

PubMed

Sun, Xueying; Zhang, Jie; Gupta, Rita; Macgibbon, Alastair K H; Kuhn-Sherlock, Barbara; Krissansen, Geoffrey W

2011-10-01

Milk fat is a natural product containing essential nutrients as well as fatty acids and other food factors with reported anti-cancer potential. Here bovine milk fat was tested for its ability to inhibit the growth of breast and colon cancers and their metastasis to the lung and liver; either alone or in combination with the chemotherapeutic agent paclitaxel. A diet containing 5% typical anhydrous milk fat (representing ~70% of the total dietary fat component) fed to Balb/c mice delayed the appearance of subcutaneous 4T1 breast and CT26 colon cancer tumours and inhibited their metastasis to the lung and liver, when compared to the control diet containing soybean oil as the only fat component. It augmented the inhibitory effects of paclitaxel on tumour growth and metastasis, and reduced the microvessel density of tumours. It displayed no apparent organ toxicity, but instead was beneficial for well-being of tumour-bearing mice by maintaining gastrocnemius muscle and epididymal adipose tissue that were otherwise depleted by cachexia. The milk fat diet ameliorated gut damage caused by paclitaxel in non-tumour-bearing mice, as evidenced by retention of jejunal morphology, villi length and intestinal γ-glutamyl transpeptidase activity, and inhibition of crypt apoptosis. It prevented loss of red and white blood cells due to both cancer-mediated immunosuppression and the cytotoxic effects of chemotherapy. The present study warrants the use of milk fat as an adjuvant to inhibit tumour metastasis during cancer chemotherapy, and to spare patients from the debilitating side-effects of cytotoxic drugs.

Effect of three cueing devices for people with Parkinson's disease with gait initiation difficulties.

PubMed

McCandless, Paula J; Evans, Brenda J; Janssen, Jessie; Selfe, James; Churchill, Andrew; Richards, Jim

2016-02-01

Freezing of gait (FOG) remains one of the most common debilitating aspects of Parkinson's disease and has been linked to injuries, falls and reduced quality of life. Although commercially available portable cueing devices exist claiming to assist with overcoming freezing; their immediate effectiveness in overcoming gait initiation failure is currently unknown. This study investigated the effects of three different types of cueing device in people with Parkinson's disease who experience freezing. Twenty participants with idiopathic Parkinson's disease who experienced freezing during gait but who were able to walk short distances indoors independently were recruited. At least three attempts at gait initiation were recorded using a 10 camera Qualisys motion analysis system and four force platforms. Test conditions were; Laser Cane, sound metronome, vibrating metronome, walking stick and no intervention. During testing 12 of the 20 participants had freezing episodes, from these participants 100 freezing and 91 non-freezing trials were recorded. Clear differences in the movement patterns were seen between freezing and non-freezing episodes. The Laser Cane was most effective cueing device at improving the forwards/backwards and side to side movement and had the least number of freezing episodes. The walking stick also showed significant improvements compared to the other conditions. The vibration metronome appeared to disrupt movement compared to the sound metronome at the same beat frequency. This study identified differences in the movement patterns between freezing episodes and non-freezing episodes, and identified immediate improvements during gait initiation when using the Laser Cane over the other interventions. Copyright © 2015. Published by Elsevier B.V.

Epoxy fatty acids mediate analgesia in murine diabetic neuropathy.

PubMed

Wagner, K; Lee, K S S; Yang, J; Hammock, B D

2017-03-01

Neuropathic pain is a debilitating condition with no adequate therapy. The health benefits of omega-3 fatty acids are established, however, the role of docosahexaenoic acid (DHA) in limiting pain has only recently been described and the mechanisms of this action remain unknown. DHA is metabolized into epoxydocosapentanoic acids (EDPs) via cytochrome P450 (CYP450) enzymes which are substrates for the soluble epoxide hydrolase (sEH) enzyme. Here, we tested several hypotheses; first, that the antinociceptive action of DHA is mediated by the EDPs. Second, based on evidence that DHA and CYP450 metabolites elicit analgesia through opioid signalling, we investigated this as a possible mechanism of action. Third, we tested whether the analgesia mediated by epoxy fatty acids had similar rewarding effects as opioid analgesics. We tested diabetic neuropathic wild-type and sEH null mice in a conditioned place preference assay for their response to EDPs, sEHI and antagonism of these treatments with naloxone, a mu-opioid receptor antagonist. The EDPs and sEH inhibitors were efficacious against chronic pain, and naloxone antagonized the action of both EDPs and sEH inhibitors. Despite this antagonism, the sEH inhibitors lacked reward side effects differing from opioids. The EpFA are analgesic against chronic pain differing from opioids which have limited efficacy in chronic conditions. EDPs and sEHI mediate analgesia in modelled chronic pain and this analgesia is blocked by naloxone. However, unlike opioids, sEHI are highly effective in neuropathic pain models and importantly lack rewarding side effects. © 2016 European Pain Federation - EFIC®.

Coping as a mediator of the relationship between stress mindset and psychological stress response: a pilot study.

PubMed

Horiuchi, Satoshi; Tsuda, Akira; Aoki, Shuntaro; Yoneda, Kenichiro; Sawaguchi, Yusuke

2018-01-01

Coping, the cognitive and behavioral effort required to manage the effects of stressors, is important in determining psychological stress responses (ie, the emotional, behavioral, and cognitive responses to stressors). Coping was classified into categories of emotional expression (eg, negative feelings and thoughts), emotional support seeking (eg, approaching loved ones to request encouragement), cognitive reinterpretation (eg, reframing a problem positively), and problem solving (eg, working to solve the problem). Stress mindset refers to the belief that stress has enhancing (stress-is-enhancing mindset) or debilitating consequences (stress-is-debilitating mindset). This study examined whether coping mediated the relationship between stress mindset and psychological stress responses. Psychological stress responses were conceptualized as depression-anxiety, irritability-anger, and helplessness. The following two hypotheses were tested: 1) a stronger stress-is-enhancing mindset is associated with less frequent use of emotional expression, emotional support seeking, and problem solving, which in turn is associated with lower levels of depression-anxiety, irritability-anger, and helplessness; 2) a stronger stress-is-debilitating mindset is associated with more frequent use of these coping strategies, which in turn is associated with higher levels of these psychological stress responses. The participants were 30 male and 94 female undergraduate and graduate students (mean age =20.4 years). Stress mindset, coping, and psychological stress responses were measured using self-report questionnaires. Six mediation analyses were performed with stress-is-enhancing mindset or stress-is-debilitating mindset as the independent variable, one of the psychological stress responses as the dependent variable, and the four coping strategies as mediators. Emotional expression partially mediated the relationship between a strong stress-is-debilitating mindset and higher irritability-anger levels. The other three coping strategies did not exhibit mediating effects. None of the coping strategies mediated the relationship between a stress-is-enhancing mindset and psychological stress responses. These results provide initial evidence that stress mindset is associated with psychological stress responses, through coping strategies.

Coping as a mediator of the relationship between stress mindset and psychological stress response: a pilot study

PubMed Central

Horiuchi, Satoshi; Tsuda, Akira; Aoki, Shuntaro; Yoneda, Kenichiro; Sawaguchi, Yusuke

2018-01-01

Background Coping, the cognitive and behavioral effort required to manage the effects of stressors, is important in determining psychological stress responses (ie, the emotional, behavioral, and cognitive responses to stressors). Coping was classified into categories of emotional expression (eg, negative feelings and thoughts), emotional support seeking (eg, approaching loved ones to request encouragement), cognitive reinterpretation (eg, reframing a problem positively), and problem solving (eg, working to solve the problem). Stress mindset refers to the belief that stress has enhancing (stress-is-enhancing mindset) or debilitating consequences (stress-is-debilitating mindset). This study examined whether coping mediated the relationship between stress mindset and psychological stress responses. Psychological stress responses were conceptualized as depression-anxiety, irritability-anger, and helplessness. The following two hypotheses were tested: 1) a stronger stress-is-enhancing mindset is associated with less frequent use of emotional expression, emotional support seeking, and problem solving, which in turn is associated with lower levels of depression-anxiety, irritability-anger, and helplessness; 2) a stronger stress-is-debilitating mindset is associated with more frequent use of these coping strategies, which in turn is associated with higher levels of these psychological stress responses. Materials and methods The participants were 30 male and 94 female undergraduate and graduate students (mean age =20.4 years). Stress mindset, coping, and psychological stress responses were measured using self-report questionnaires. Six mediation analyses were performed with stress-is-enhancing mindset or stress-is-debilitating mindset as the independent variable, one of the psychological stress responses as the dependent variable, and the four coping strategies as mediators. Results Emotional expression partially mediated the relationship between a strong stress-is-debilitating mindset and higher irritability-anger levels. The other three coping strategies did not exhibit mediating effects. None of the coping strategies mediated the relationship between a stress-is-enhancing mindset and psychological stress responses. Conclusion These results provide initial evidence that stress mindset is associated with psychological stress responses, through coping strategies. PMID:29535562

Irinotecan-induced mucositis: the interactions and potential role of GLP-2 analogues.

PubMed

Mayo, Bronwen J; Stringer, Andrea M; Bowen, Joanne M; Bateman, Emma H; Keefe, Dorothy M

2017-02-01

A common side effect of irinotecan administration is gastrointestinal mucositis, often manifesting as severe diarrhoea. The damage to the structure and function of the gastrointestinal tract caused by this cytotoxic agent is debilitating and often leads to alterations in patients' regimens, hospitalisation or stoppage of treatment. The purpose of this review is to identify mechanisms of irinotecan-induced intestinal damage and a potential role for GLP-2 analogues for intervention. This is a review of current literature on irinotecan-induced mucositis and GLP-2 analogues mechanisms of action. Recent studies have found alterations that appear to be crucial in the development of severe intestinal mucositis, including early apoptosis, alterations in proliferation and cell survival pathways, as well as induction of inflammatory cascades. Several studies have indicated a possible role for glucagon-like peptide-2 analogues in treating this toxicity, due to its proven intestinotrophic, anti-apoptotic and anti-inflammatory effects in other models of gastrointestinal disease. This review provides evidence as to why and how this treatment may improve mucositis through the possible molecular crosstalk that may be occurring in models of severe intestinal mucositis.

Plasma Membrane Proteomics of Human Breast Cancer Cell Lines Identifies Potential Targets for Breast Cancer Diagnosis and Treatment

PubMed Central

Ziegler, Yvonne S.; Moresco, James J.; Tu, Patricia G.; Yates, John R.; Nardulli, Ann M.

2014-01-01

The use of broad spectrum chemotherapeutic agents to treat breast cancer results in substantial and debilitating side effects, necessitating the development of targeted therapies to limit tumor proliferation and prevent metastasis. In recent years, the list of approved targeted therapies has expanded, and it includes both monoclonal antibodies and small molecule inhibitors that interfere with key proteins involved in the uncontrolled growth and migration of cancer cells. The targeting of plasma membrane proteins has been most successful to date, and this is reflected in the large representation of these proteins as targets of newer therapies. In view of these facts, experiments were designed to investigate the plasma membrane proteome of a variety of human breast cancer cell lines representing hormone-responsive, ErbB2 over-expressing and triple negative cell types, as well as a benign control. Plasma membranes were isolated by using an aqueous two-phase system, and the resulting proteins were subjected to mass spectrometry analysis. Overall, each of the cell lines expressed some unique proteins, and a number of proteins were expressed in multiple cell lines, but in patterns that did not always follow traditional clinical definitions of breast cancer type. From our data, it can be deduced that most cancer cells possess multiple strategies to promote uncontrolled growth, reflected in aberrant expression of tyrosine kinases, cellular adhesion molecules, and structural proteins. Our data set provides a very rich and complex picture of plasma membrane proteins present on breast cancer cells, and the sorting and categorizing of this data provides interesting insights into the biology, classification, and potential treatment of this prevalent and debilitating disease. PMID:25029196

Combined cannabinoid therapy via an oromucosal spray.

PubMed

Perez, Jordi

2006-08-01

Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). It is recognized that a significant proportion of patients suffering with the debilitating symptoms of pain and spasticity in multiple sclerosis or other conditions smoke cannabis despite the legal implications and stigma associated with this controlled substance. GW Pharmaceuticals have developed Sativex (GW- 1,000-02), a combined cannabinoid medicine that delivers and maintains therapeutic levels of two principal cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), via an oromucosal pump spray, that aims to minimize psychotropic side effects. Sativex has proved to be well tolerated and successfully self-administered and self-titrated in both healthy volunteers and patient cohorts. Clinical assessment of this combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.

A comparative analysis of longitudinal computed tomography and histopathology for evaluating the potential of mesenchymal stem cells in mitigating radiation-induced pulmonary fibrosis.

PubMed

Perez, Jessica R; Lee, Sangkyu; Ybarra, Norma; Maria, Ola; Serban, Monica; Jeyaseelan, Krishinima; Wang, Li Ming; Seuntjens, Jan; Naqa, Issam El

2017-08-22

Radiation-induced pulmonary fibrosis (RIPF) is a debilitating side effect that occurs in up to 30% of thoracic irradiations in breast and lung cancer patients. RIPF remains a major limiting factor to dose escalation and an obstacle to applying more promising new treatments for cancer cure. Limited treatment options are available to mitigate RIPF once it occurs, but recently, mesenchymal stem cells (MSCs) and a drug treatment stimulating endogenous stem cells (GM-CSF) have been investigated for their potential in preventing this disease onset. In a pre-clinical rat model, we contrasted the application of longitudinal computed tomography (CT) imaging and classical histopathology to quantify RIPF and to evaluate the potential of MSCs in mitigating RIPF. Our results on histology demonstrate promises when MSCs are injected endotracheally (but not intravenously). While our CT analysis highlights the potential of GM-CSF treatment. Advantages and limitations of both analytical methods are contrasted in the context of RIPF.

Psychoanalysis: the sacred and the profane.

PubMed

Frosch, Allan

2014-06-01

Colleagues from a variety of perspectives have written about the propensity to enshrine psychoanalytic theory. The meaning of the word "enshrine" is to cherish as sacred an idea or philosophy and protect it from change. In other words, the way we view psychoanalysis, our theories of mind and technique, become holy writ and we have divided the world of theory into the sacred and the profane. This is the kiss of death for theory, which must constantly evolve and change, but comforting for the analyst who believes he is on the side of the right, the sacred. In this paper I will discuss how our propensity to enshrine theory has had a debilitating effect on the development of psychoanalysis and, in particular, as a treatment for the most vulnerable people who seek our help. I also address the idea that movement away from enshrined positions allows us to construct different versions of reality. In this context, the notion of "action at a distance" is presented along with the attendant idea of psychoanalytic entanglement.

A Systematic Review of the Safety and Effect of Neurofeedback on Fatigue and Cognition.

PubMed

Luctkar-Flude, Marian; Groll, Dianne

2015-07-01

Many cancer survivors continue to experience ongoing symptoms, such as fatigue and cognitive impairment, which are poorly managed and have few effective, evidence-based treatment options. Neurofeedback is a noninvasive, drug-free form of brain training that may alleviate long-term symptoms reported by cancer patients. The purpose of this systematic review of the literature was to describe the effectiveness and safety of neurofeedback for managing fatigue and cognitive impairment. A systematic review of the literature was conducted using Joanna Briggs Institute (JBI) methodology. A comprehensive search of 5 databases was conducted: Medline, CINAHL, AMED, PsycInfo, and Embase. Randomized and nonrandomized controlled trials, controlled before and after studies, cohort, case control studies, and descriptive studies were included in this review. Twenty-seven relevant studies were included in the critical appraisals. The quality of most studies was poor to moderate based on the JBI critical appraisal checklists. Seventeen studies were deemed of sufficient quality to be included in the review: 10 experimental studies and 7 descriptive studies. Of these, only 2 were rated as high-quality studies and the remaining were rated as moderate quality. All 17 included studies reported positive results for at least one fatigue or cognitive outcome in a variety of populations, including 1 study with breast cancer survivors. Neurofeedback interventions were well tolerated with only 3 studies reporting any side effects. Despite issues with methodological quality, the overall positive findings and few reported side effects suggest neurofeedback could be helpful in alleviating fatigue and cognitive impairment. Currently, there is insufficient evidence that neurofeedback is an effective therapy for management of these symptoms in cancer survivors, however, these promising results support the need for further research with this patient population. More information about which neurofeedback technologies, approaches, and protocols could be successfully used with cancer survivors and with minimal side effects is needed. This research will have significance to nurses and physicians in oncology and primary care settings who provide follow-up care and counseling to cancer survivors experiencing debilitating symptoms in order to provide information and education related to evidence-based therapy options. © The Author(s) 2015.

21 CFR 312.84 - Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and...

Code of Federal Regulations, 2013 CFR

2013-04-01

... applications for drugs to treat life-threatening and severely-debilitating illnesses. 312.84 Section 312.84... Severely-debilitating Illnesses § 312.84 Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and severely-debilitating illnesses. (a) FDA's application of the...

21 CFR 312.84 - Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and...

Code of Federal Regulations, 2014 CFR

2014-04-01

... applications for drugs to treat life-threatening and severely-debilitating illnesses. 312.84 Section 312.84... Severely-debilitating Illnesses § 312.84 Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and severely-debilitating illnesses. (a) FDA's application of the...

21 CFR 312.84 - Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and...

Code of Federal Regulations, 2011 CFR

2011-04-01

... applications for drugs to treat life-threatening and severely-debilitating illnesses. 312.84 Section 312.84... Severely-debilitating Illnesses § 312.84 Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and severely-debilitating illnesses. (a) FDA's application of the...

21 CFR 312.84 - Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and...

Code of Federal Regulations, 2012 CFR

2012-04-01

... applications for drugs to treat life-threatening and severely-debilitating illnesses. 312.84 Section 312.84... Severely-debilitating Illnesses § 312.84 Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and severely-debilitating illnesses. (a) FDA's application of the...

A Comparison of Traditional and Self-Control Desensitization.

ERIC Educational Resources Information Center

Deffenbacher, Jerry L.; Parks, Donald H.

1979-01-01

Compared effectiveness of counterconditioning and self-control models of systematic desensitization in reducing targeted and nontargeted anxieties. Treatments were equally effective in reducing and maintaining reduction of targeted anxiety, debilitating test anxiety. (Author)

Study design and protocol for a culturally adapted cognitive behavioral stress and self-management intervention for localized prostate cancer: The Encuentros de Salud study.

PubMed

Penedo, Frank J; Antoni, Michael H; Moreno, Patricia I; Traeger, Lara; Perdomo, Dolores; Dahn, Jason; Miller, Gregory E; Cole, Steve; Orjuela, Julian; Pizarro, Edgar; Yanez, Betina

2018-06-14

Almost 2.8 million men in the U.S. are living with prostate cancer (PC), accounting for 40% of all male cancer survivors. Men diagnosed with prostate cancer may experience chronic and debilitating treatment side effects, including sexual and urinary dysfunction, pain and fatigue. Side effects can be stressful and can also lead to poor psychosocial functioning. Prior trials reveal that group-based cognitive behavioral stress and self-management (CBSM) is effective in reducing stress and mitigating some of these symptoms, yet little is known about the effects of culturally-translated CBSM among Spanish-speaking men with PC. This manuscript describes the rationale and study design of a multi-site, randomized controlled trial to determine whether participation in a culturally adapted cognitive behavioral stress management (C-CBSM) intervention leads to significantly greater reductions in symptom burden and improvements in health-related quality of life relative to participation in a non-culturally adapted cognitive behavioral stress management (CBSM) intervention. Participants (N = 260) will be Spanish-speaking Hispanic/Latino men randomized to the standard, non-culturally adapted CBSM intervention (e.g., cognitive behavioral strategies, stress management, and health maintenance) or the culturally adapted C-CBSM intervention (e.g., content adapted to be compatible with Hispanic/Latino cultural patterns and belief systems, meanings, values and social context) for 10 weeks. Primary outcomes (i.e., disease-specific symptom burden and health-related quality of life) will be assessed across time. We hypothesize that a culturally adapted C-CBSM intervention will be more efficacious in reducing symptom burden and improving health-related quality of life among Hispanic/Latino men when compared to a non-culturally adapted CBSM intervention. Copyright © 2017. Published by Elsevier Inc.

Effects of ECT in treatment of depression: study protocol for a prospective neuroradiological study of acute and longitudinal effects on brain structure and function.

PubMed

Oltedal, Leif; Kessler, Ute; Ersland, Lars; Grüner, Renate; Andreassen, Ole A; Haavik, Jan; Hoff, Per Ivar; Hammar, Åsa; Dale, Anders M; Hugdahl, Kenneth; Oedegaard, Ketil J

2015-05-01

Major depression can be a serious and debilitating condition. For some patients in a treatment resistant depressive episode, electroconvulsive treatment (ECT) is the only treatment that is effective. Although ECT has shown efficacy in randomized controlled trials, the treatment is still controversial and stigmatized. This can in part be attributed to our lack of knowledge of the mechanisms of action. Some reports also suggest potential harmful effects of ECT treatment and memory related side effects have been documented. The present study will apply state of the art radiology through advanced magnetic resonance imaging (MRI) techniques to investigate structural and functional brain effects of ECT. As a multi-disciplinary collaboration, imaging findings will be correlated to psychiatric response parameters, neuropsychological functioning as well as neurochemical and genetic biomarkers that can elucidate the underlying mechanisms. The aim is to document both treatment effects and potential harmful effects of ECT. n = 40 patients in a major depressive episode (bipolar and major depressive disorder). Two control groups with n = 15 in each group: age and gender matched healthy volunteers not receiving ECT and patients undergoing electrical cardioversion (ECV) for atrial fibrillation (AF). Observation time: six months. The study will contribute to our understanding of the pathophysiology of major depression as well as mechanisms of action for the most effective treatment for the disorder; ECT.

A New Orally Active, Aminothiol Radioprotector-Free of Nausea and Hypotension Side Effects at Its Highest Radioprotective Doses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soref, Cheryl M.; Hacker, Timothy A.; Fahl, William E., E-mail: fahl@oncology.wisc.edu

Purpose: A new aminothiol, PrC-210, was tested for orally conferred radioprotection (rats, mice; 9.0 Gy whole-body, which was otherwise lethal to 100% of the animals) and presence of the debilitating side effects (nausea/vomiting, hypotension/fainting) that restrict use of the current aminothiol, amifostine (Ethyol, WR-2721). Methods and Materials: PrC-210 in water was administered to rats and mice at times before irradiation, and percent-survival was recorded for 60 days. Subcutaneous (SC) amifostine (positive control) or SC PrC-210 was administered to ferrets (Mustela putorius furo) and retching/emesis responses were recorded. Intraperitoneal amifostine (positive control) or PrC-210 was administered to arterial cannulated rats tomore » score drug-induced hypotension. Results: Oral PrC-210 conferred 100% survival in rat and mouse models against an otherwise 100% lethal whole-body radiation dose (9.0 Gy). Oral PrC-210, administered by gavage 30-90 min before irradiation, conferred a broad window of radioprotection. The comparison of PrC-210 and amifostine side effects was striking because there was no retching or emesis in 10 ferrets treated with PrC-210 and no induced hypotension in arterial cannulated rats treated with PrC-210. The tested PrC-210 doses were the ferret and rat equivalent doses of the 0.5 maximum tolerated dose (MTD) PrC-210 dose in mice. The human equivalent of this mouse 0.5 MTD PrC-210 dose would likely be the highest PrC-210 dose used in humans. By comparison, the mouse 0.5 MTD amifostine dose, 400 {mu}g/g body weight (equivalent to the human amifostine dose of 910 mg/m{sup 2}), when tested at equivalent ferret and rat doses in the above models produced 100% retching/vomiting in ferrets and 100% incidence of significant, progressive hypotension in rats. Conclusions: The PrC-210 aminothiol, with no detectable nausea/vomiting or hypotension side effects in these preclinical models, is a logical candidate for human drug development to use in healthy humans in a wide variety of radioprotection settings, including medical radiation, space travel, and nuclear accidents.« less

Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Dental pathologies and osteoradionecrosis (Part 1) literature review and consensus statement.

PubMed

Buglione, Michela; Cavagnini, Roberta; Di Rosario, Federico; Sottocornola, Lara; Maddalo, Marta; Vassalli, Lucia; Grisanti, Salvatore; Salgarello, Stefano; Orlandi, Ester; Paganelli, Corrado; Majorana, Alessandra; Gastaldi, Giorgio; Bossi, Paolo; Berruti, Alfredo; Pavanato, Giovanni; Nicolai, Piero; Maroldi, Roberto; Barasch, Andrei; Russi, Elvio G; Raber-Durlacher, Judith; Murphy, Barbara; Magrini, Stefano M

2016-01-01

Radiotherapy alone or in combination with chemotherapy and/or surgery is the typical treatment for head and neck cancer patients. Acute side effects (such as oral mucositis, dermatitis, salivary changes, taste alterations, etc.), and late toxicities in particular (such as osteo-radionecrosis, hypo-salivation and xerostomia, trismus, radiation caries etc.), are often debilitating. These effects tend to be underestimated and insufficiently addressed in the medical community. A multidisciplinary group of head and neck cancer specialists met in Milan with the aim of reaching a consensus on clinical definitions and management of these toxicities. The Delphi Appropriateness method was used for developing the consensus, and external experts evaluated the conclusions. This paper contains 10 clusters of statements about the clinical definitions and management of head and neck cancer treatment sequels (dental pathologies and osteo-radionecroses) that reached consensus, and offers a review of the literature about these topics. The review was split into two parts: the first part dealt with dental pathologies and osteo-radionecroses (10 clusters of statements), whereas this second part deals with trismus and xerostomia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Quercetin targets the interaction of calcineurin with LxVP-type motifs in immunosuppression

PubMed Central

Zhao, Yane; Zhang, Jin; Shi, Xiaoyu; Li, Jing; Wang, Rui; Song, Ruiwen; Wei, Qun; Cai, Huaibin; Luo, Jing

2016-01-01

Calcineurin (CN) is a unique calcium/calmodulin (CaM)-activated serine/threonine phosphatase. To perform its diverse biological functions, CN communicates with many substrates and other proteins. In the physiological activation of T cells, CN acts through transcriptional factors belonging to the NFAT family and other transcriptional effectors. The classic immunosuppressive drug cyclosporin A (CsA) can bind to cyclophilin (CyP) and compete with CN for the NFAT LxVP motif. CsA has debilitating side effects, including nephrotoxicity, hypertension and tremor. It is desirable to develop alternative immunosuppressive agents. To this end, we first tested the interactions between CN and the LxVP-type substrates, including endogenous regulators of calcineurin (RCAN1) and NFAT. Interestingly, we found that quercetin, the primary dietary flavonol, can inhibit the activity of CN and significantly disrupt the associations between CN and its LxVP-type substrates. We then validated the inhibitory effects of quercetin on the CN-NFAT interactions in cell-based assays. Further, quercetin also shows dose-dependent suppression of cytokine gene expression in mouse spleen cells. These data raise the possibility that the interactions of CN with its LxVP-type substrates are potential targets for immunosuppressive agents. PMID:27109380

Drugs in development for toxoplasmosis: advances, challenges, and current status.

PubMed

Alday, P Holland; Doggett, Joseph Stone

2017-01-01

Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis.

Effective management of an advanced gastric cancer patient by TS-1 combined chemotherapy using nasojejunal tube and successful transfer to home care after percutaneous transesophageal gastro-tubing (PTEG): a case report.

PubMed

Okita, Atsushi; Miyade, Yoshio; Okano, Kazuo

2010-02-01

A 67-year-old woman with debilitation and massive ascites was admitted to our hospital and diagnosed with stage IV scirrhous gastric cancer with peritoneal dissemination. After successful nasojejunal tube feeding because of oral intake disability, TS-1 combined with paclitaxel chemotherapy was selected. TS-1 at 80mg/m2 was given daily via nasojejunal tube for 2 weeks, followed by a 1-week rest, and paclitaxel at 50mg/m2 was administered intravenously on day 1 and 8. There were no serious side effects. After 4 cycles, a partial response was observed and percutaneous transesophageal gastrotubing (PTEG) was placed. After the fifth cycle, she was transferred to her home and received chemotherapy in an outpatient clinic. After 7 cycles, the disease progressed, and TS-1 combined with low-dose cisplatin was administered for 3 cycles. However, the patient died 16 weeks after discharge. PTEG was useful not only for a route of TS-1 administration, but also for receiving chemotherapy at home to maintain her quality.

Drugs in development for toxoplasmosis: advances, challenges, and current status

PubMed Central

Alday, P Holland; Doggett, Joseph Stone

2017-01-01

Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis. PMID:28182168

Fast-scan cyclic voltammetry demonstrates that L-DOPA produces dose-dependent regionally selective, bimodal effects on striatal dopamine kinetics in vivo.

PubMed

Harun, R; Hare, K M; Brough, M E; Munoz, M J; Grassi, C M; Torres, G E; Grace, A A; Wagner, A K

2015-11-27

Parkinson's disease (PD) is a debilitating condition that is caused by a relatively specific degeneration of dopaminergic (DAergic) neurons of the substantia nigra pars compacta. Levodopa (L-DOPA) was introduced as a viable treatment option for PD over 40 years ago and still remains the most common and effective therapy for PD. Though the effects of L-DOPA to augment striatal DA production are well known, little is actually known about how L-DOPA alters the kinetics of DA neurotransmission that contribute to its beneficial and adverse effects. In this study, we examined the effects of L-DOPA administration (50mg/kg carbidopa + 0, 100, and 250mg/kg L-DOPA) on regional electrically stimulated DA response kinetics using fast-scan cyclic voltammetry (FSCV) in anesthetized rats. We demonstrate that L-DOPA enhances DA release in both the dorsal striatum (D-STR) and nucleus accumbens (NAc), but surprisingly causes a delayed inhibition of release in the D-STR. In both regions, L-DOPA progressively attenuated reuptake kinetics, predominantly through a decrease in Vmax. These findings have important implications on understanding the pharmacodynamics of L-DOPA, which can be informative for understand its therapeutic effects and also common side effects like L-DOPA induced dyskinesias (LID). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Debilitating beliefs and emotional distress in patients given immunotherapy for insect sting allergy: a prospective study.

PubMed

Confino-Cohen, Ronit; Melamed, Samuel; Goldberg, Arnon

2009-01-01

Patients who receive venom immunotherapy (VIT) for systemic reactions (SRs) to insect stings are advised that once they reach the maintenance dose they are almost 100% protected against future SRs. However, initial evidence indicates that some patients continue to perceive themselves as highly debilitated by the allergy and are preoccupied with the allergic event. These factors have significant impact on their emotional well-being and allergy-related quality of life (ARQOL). We aimed to explore prospectively whether patients would experience these adverse psychological outcomes after receiving VIT coupled with professional explanation and reassurance of protection. Thirty-four patients who received VIT for systemic insect allergy and were under close medical surveillance were included. Before and 1 year after initiation of treatment, patients completed a questionnaire that measured debilitating beliefs, preoccupation with the SR event, emotional distress ARQOL, and QOL in general. Physician-graded severity of the reaction was recorded as well. VIT had a beneficial effect on all allergy-related variables. Self-imposed debilitating beliefs, preoccupation with the anaphylactic event, and ARQOL significantly but modestly improved over time. No association was found between ARQOL and QOL in general. The later variable as well as emotional distress remained unchanged after the VIT. This study shows that patients with sting allergy guided by trained personnel and treated with VIT show a reduction in dysfunctional beliefs and an improvement in ARQOL. Disputing medically unfounded beliefs that persist in some patients might improve their ARQOL.

Human pancreatic cancer xenografts recapitulate key aspects of cancer cachexia.

PubMed

Delitto, Daniel; Judge, Sarah M; Delitto, Andrea E; Nosacka, Rachel L; Rocha, Fernanda G; DiVita, Bayli B; Gerber, Michael H; George, Thomas J; Behrns, Kevin E; Hughes, Steven J; Wallet, Shannon M; Judge, Andrew R; Trevino, Jose G

2017-01-03

Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia. Specifically, human PC xenografts were generated by implantation of pancreatic cancer cells, L3.6pl and PANC-1, either in the flank or orthotopically within the pancreas. Mice bearing orthotopic xenografts demonstrated significant muscle wasting and atrophy-associated gene expression changes compared to controls. Further, despite the absence of adaptive immunity, splenic tissue from orthotopically engrafted mice demonstrated elevations in several pro-inflammatory cytokines associated with cancer cachexia, including TNFα, IL1β, IL6 and KC (murine IL8 homologue), when compared to controls. Therefore, data presented here support further investigation into the complexity of cancer cachexia in PC to identify potential targets for this debilitating syndrome.

Nutrient supplementation approaches in the treatment of ADHD.

PubMed

Rucklidge, Julia J; Johnstone, Jeanette; Kaplan, Bonnie J

2009-04-01

Attention-deficit/hyperactivity disorder (ADHD) is a chronic, debilitating psychiatric illness that often co-occurs with other common psychiatric problems. Although empirical evidence supports pharmacological and behavioral treatments, side effects, concerns regarding safety and fears about long-term use all contribute to families searching for alternative methods of treating the symptoms of ADHD. This review presents the published evidence on supplementation, including single ingredients (e.g., minerals, vitamins, amino acids and essential fatty acids), botanicals and multi-ingredient formulas in the treatment of ADHD symptoms. In most cases, evidence is sparse, mixed and lacking information. Of those supplements where we found published studies, the evidence is best for zinc (two positive randomized, controlled trials); there is mixed evidence for carnitine, pycnogenol and essential fatty acids, and more research is needed before drawing conclusions about vitamins, magnesium, iron, SAM-e, tryptophan and Ginkgo biloba with ginseng. To date, there is no evidence to support the use of St John's wort, tyrosine or phenylalanine in the treatment of ADHD symptoms. Multi-ingredient approaches are an intriguing yet under-researched area; we discuss the benefits of this approach considering the heterogeneous nature of ADHD.

Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease.

PubMed

Bastide, Matthieu F; Meissner, Wassilios G; Picconi, Barbara; Fasano, Stefania; Fernagut, Pierre-Olivier; Feyder, Michael; Francardo, Veronica; Alcacer, Cristina; Ding, Yunmin; Brambilla, Riccardo; Fisone, Gilberto; Jon Stoessl, A; Bourdenx, Mathieu; Engeln, Michel; Navailles, Sylvia; De Deurwaerdère, Philippe; Ko, Wai Kin D; Simola, Nicola; Morelli, Micaela; Groc, Laurent; Rodriguez, Maria-Cruz; Gurevich, Eugenia V; Quik, Maryka; Morari, Michele; Mellone, Manuela; Gardoni, Fabrizio; Tronci, Elisabetta; Guehl, Dominique; Tison, François; Crossman, Alan R; Kang, Un Jung; Steece-Collier, Kathy; Fox, Susan; Carta, Manolo; Angela Cenci, M; Bézard, Erwan

2015-09-01

Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia (LID) are ultimately experienced by the vast majority of patients. In addition, psychiatric conditions often manifested as compulsive behaviours, are emerging as a serious problem in the management of L-dopa therapy. The present review attempts to provide an overview of our current understanding of dyskinesia and other L-dopa-induced dysfunctions, a field that dramatically evolved in the past twenty years. In view of the extensive literature on LID, there appeared a critical need to re-frame the concepts, to highlight the most suitable models, to review the central nervous system (CNS) circuitry that may be involved, and to propose a pathophysiological framework was timely and necessary. An updated review to clarify our understanding of LID and other L-dopa-related side effects was therefore timely and necessary. This review should help in the development of novel therapeutic strategies aimed at preventing the generation of dyskinetic symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Xerostomia and trismus (Part 2). Literature review and consensus statement.

PubMed

Buglione, Michela; Cavagnini, Roberta; Di Rosario, Federico; Maddalo, Marta; Vassalli, Lucia; Grisanti, Salvatore; Salgarello, Stefano; Orlandi, Ester; Bossi, Paolo; Majorana, Alessandra; Gastaldi, Giorgio; Berruti, Alfredo; Trippa, Fabio; Nicolai, Pietro; Barasch, Andrei; Russi, Elvio G; Raber-Durlacher, Judith; Murphy, Barbara; Magrini, Stefano M

2016-06-01

Radiotherapy alone or in combination with chemotherapy and/or surgery is a well-known radical treatment for head and neck cancer patients. Nevertheless acute side effects (such as moist desquamation, skin erythema, loss of taste, mucositis etc.) and in particular late toxicities (osteoradionecrosis, xerostomia, trismus, radiation caries etc.) are often debilitating and underestimated. A multidisciplinary group of head and neck cancer specialists from Italy met in Milan with the aim of reaching a consensus on a clinical definition and management of these toxicities. The Delphi Appropriateness method was used for this consensus and external experts evaluated the conclusions. The paper contains 20 clusters of statements about the clinical definition and management of stomatological issues that reached consensus, and offers a review of the literature about these topics. The review was split into two parts: the first part dealt with dental pathologies and osteo-radionecrosis (10 clusters of statements), whereas this second part deals with trismus and xerostomia (10 clusters of statements). Copyright © 2016. Published by Elsevier Ireland Ltd.

Current Treatment Limitations in Age-Related Macular Degeneration and Future Approaches Based on Cell Therapy and Tissue Engineering

PubMed Central

Fernández-Robredo, P.; Sancho, A.; Johnen, S.; Recalde, S.; Gama, N.; Thumann, G.; Groll, J.; García-Layana, A.

2014-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein. PMID:24672707

Nanotechnology-Based Detection and Targeted Therapy in Cancer: Nano-Bio Paradigms and Applications

PubMed Central

Mousa, Shaker A.; Bharali, Dhruba J.

2011-01-01

The application of nanotechnology to biomedicine, particularly in cancer diagnosis and treatment, promises to have a profound impact on healthcare. The exploitation of the unique properties of nano-sized particles for cancer therapeutics is most popularly known as nanomedicine. The goals of this review are to discuss the current state of nanomedicine in the field of cancer detection and the subsequent application of nanotechnology to treatment. Current cancer detection methods rely on the patient contacting their provider when they feel ill, or relying on non-specific screening methods, which unfortunately often result in cancers being detected only after it is too late for effective treatment. Cancer treatment paradigms mainly rely on whole body treatment with chemotherapy agents, exposing the patient to medications that non-specifically kill rapidly dividing cells, leading to debilitating side effects. In addition, the use of toxic organic solvents/excipients can hamper the further effectiveness of the anticancer drug. Nanomedicine has the potential to increase the specificity of treatment of cancer cells while leaving healthy cells intact through the use of novel nanoparticles. This review discusses the use of nanoparticles such as quantum dots, nanoshells, nanocrystals, nanocells, and dendrimers for the detection and treatment of cancer. Future directions and perspectives of this cutting-edge technology are also discussed. PMID:24212938

Case report: Emergency department diagnosis of melorheostosis in the upper extremity: a rare disease with an unusual presentation.

PubMed

Murano, Tiffany; Egarian, Michele

2012-10-01

Melorheostosis is a rare disease that affects fewer than 1:1,000,000 persons worldwide and most typically affects the lower extremities. It is a non-hereditary disease that may be debilitating due to chronic pain, contractures of the soft tissue, and even shortening of the affected limbs. Although it most commonly occurs in the lower extremities, melorheostosis has been reported in various locations throughout the body. This case report describes a patient who presented to the Emergency Department (ED) with this rare disease in an uncommonly affected bone. The patient was a 21-year-old man who presented to the ED with pain in his left upper extremity that he attributed to playing sports 3 days before presentation. Plain films revealed periosteal hyperostosis typical of melorheostosis in several of his carpals, metacarpals, and phalanges, as well as the humerus and ulna. The patient was discharged with orthopedic follow-up and pain medication. Melorheostosis is a rare disease that has characteristic radiographic findings likened to the appearance of melting wax flowing down the side of a candle. In certain cases, the disease can be debilitating and may require chronic pain management and even operative intervention. If this diagnosis is made in the ED, the emergency physician should provide adequate pain management and refer the patient to an orthopedic specialist for a work-up to rule out other sclerosing bone dysplasias. Copyright © 2012 Elsevier Inc. All rights reserved.

The Intramuscular Course of the Greater Occipital Nerve: Novel Findings with Potential Implications for Operative Interventions and Occipital Neuralgia

PubMed Central

Tubbs, R. Shane; Watanabe, Koichi; Loukas, Marios; Cohen-Gadol, Aaron A.

2014-01-01

Background: A better understanding of the etiologies of occipital neuralgia would help the clinician treat patients with this debilitating condition. Since few studies have examined the muscular course of the greater occipital nerve (GON), this study was performed. Methods: Thirty adult cadaveric sides underwent dissection of the posterior occiput with special attention to the intramuscular course of the GON. Nerves were typed based on their muscular course. Results: The GON traveled through the trapezius (type I; n = 5, 16.7%) or its aponeurosis (type II; n = 15, 83.3%) to become subcutaneous. Variations in the subtrapezius muscular course were found in 10 (33%) sides. In two (6.7%) sides, the GON traveled through the lower edge of the inferior capitis oblique muscle (subtype a). On five (16.7%) sides, the GON coursed through a tendinous band of the semispinalis capitis, not through its muscular fibers (subtype b). On three (10%) sides the GON bypassed the semispinalis capitis muscle to travel between its most medial fibers and the nuchal ligament (subtype c). For subtypes, eight were type II courses (through the aponeurosis of the trapezius), and two were type I courses (through the trapezius muscle). The authors identified two type IIa courses, four type IIb courses, and two type IIc courses. Type I courses included one type Ib and one type Ic courses. Conclusions: Variations in the muscular course of the GON were common. Future studies correlating these findings with the anatomy in patients with occipital neuralgia may elucidate nerve courses vulnerable to nerve compression. This enhanced classification scheme describes the morphology in this region and allows more specific communications about GON variations. PMID:25422783

Orally active Epac inhibitor reverses mechanical allodynia and loss of intraepidermal nerve fibers in a mouse model of chemotherapy-induced peripheral neuropathy.

PubMed

Singhmar, Pooja; Huo, XiaoJiao; Li, Yan; Dougherty, Patrick M; Mei, Fang; Cheng, Xiaodong; Heijnen, Cobi J; Kavelaars, Annemieke

2018-05-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of cancer treatment that significantly compromises quality of life of cancer patients and survivors. Identification of targets for pharmacological intervention to prevent or reverse CIPN is needed. We investigated exchange protein regulated by cAMP (Epac) as a potential target. Epacs are cAMP-binding proteins known to play a pivotal role in mechanical allodynia induced by nerve injury and inflammation. We demonstrate that global Epac1-knockout (Epac1-/-) male and female mice are protected against paclitaxel-induced mechanical allodynia. In addition, spinal cord astrocyte activation and intraepidermal nerve fiber (IENF) loss are significantly reduced in Epac1-/- mice as compared to wild-type mice. Moreover, Epac1-/- mice do not develop the paclitaxel-induced deficits in mitochondrial bioenergetics in the sciatic nerve that are a hallmark of CIPN. Notably, mice with cell-specific deletion of Epac1 in Nav1.8-positive neurons (N-Epac1-/-) also show reduced paclitaxel-induced mechanical allodynia, astrocyte activation, and IENF loss, indicating that CIPN develops downstream of Epac1 activation in nociceptors. The Epac-inhibitor ESI-09 reversed established paclitaxel-induced mechanical allodynia in wild-type mice even when dosing started 10 days after completion of paclitaxel treatment. In addition, oral administration of ESI-09 suppressed spinal cord astrocyte activation in the spinal cord and protected against IENF loss. Ex vivo, ESI-09 blocked paclitaxel-induced abnormal spontaneous discharges in dorsal root ganglion neurons. Collectively, these findings implicate Epac1 in nociceptors as a novel target for treatment of CIPN. This is clinically relevant because ESI-09 has the potential to reverse a debilitating and long-lasting side effect of cancer treatment.

Efficacy of Complementary Therapies in the Quality of Life of Breast Cancer Survivors

PubMed Central

Zaidi, Sahar; Hussain, Showket; Verma, Shalini; Veqar, Zubia; Khan, Asiya; Nazir, Sheeraz Un; Singh, Neha; Moiz, Jamal Ali; Tanwar, Pranay; Srivastava, Anurag; Rath, G. K.; Mehrotra, Ravi

2018-01-01

Breast cancer (BC) is the most common cancer diagnosed in women and the second most common cancer overall, ranking as the fifth cause of death from cancer. The chronicity of the disease produces long-term physiological and psychological manifestations, which adversely affect the quality of life of the individual. The primary treatment while managing cancer presents with various debilitating side effects. With the recent advances in treatment techniques that have improved the survival rate, patients suffer from continuing posttreatment complications. Patients seem to cope well with the stress of treatment of BC and sustain a normal life; however, the deterioration in physical well-being makes the patient functionally inefficient. Exercise has been proven to be an effective, safe, and feasible tool in combating the adverse effects of treatment, prevents complications and decreases the risk of BC-specific mortality. This review briefly presents an overview of the burden of the disease and its management strategies. Owing to the heterogeneity of the population and the multitude of therapies they receive, the response of each patient to treatment is different and so is the magnitude of adverse effects. The review discusses the late sequelae following treatment and evidence supporting the role of physical activity in their management. In conclusion, there is a need for personalized physical activity plans to be developed to suit the individual and their circumstances. PMID:29376027

The Effect of Migraine Headache on Educational Attainment

ERIC Educational Resources Information Center

Rees, Daniel I.; Sabia, Joseph J.

2011-01-01

Despite the fact that migraine headaches are common and debilitating, little is known about their effect on educational attainment. Using data drawn from the National Longitudinal Study of Adolescent Health, we estimate the relationship between migraine headache and three outcomes: high school grade point average, the probability of graduating…

Zidovudine ameliorates pathology in the mouse model of Duchenne muscular dystrophy via P2RX7 purinoceptor antagonism.

PubMed

Al-Khalidi, Rasha; Panicucci, Chiara; Cox, Paul; Chira, Natalia; Róg, Justyna; Young, Christopher N J; McGeehan, Rhiannon E; Ambati, Kameshwari; Ambati, Jayakrishna; Zabłocki, Krzysztof; Gazzerro, Elisabetta; Arkle, Stephen; Bruno, Claudio; Górecki, Dariusz C

2018-04-11

Duchenne muscular dystrophy (DMD) is the most common inherited muscle disorder that causes severe disability and death of young men. This disease is characterized by progressive muscle degeneration aggravated by sterile inflammation and is also associated with cognitive impairment and low bone density. Given that no current treatment can improve the long-term outcome, approaches with a strong translational potential are urgently needed. Duchenne muscular dystrophy (DMD) alters P2RX7 signaling in both muscle and inflammatory cells and inhibition of this receptor resulted in a significant attenuation of muscle and non-muscle symptoms in DMD mdx mouse model. As P2RX7 is an attractive target in a range of human diseases, specific antagonists have been developed. Yet, these will require lengthy safety testing in the pediatric population of Duchenne muscular dystrophy (DMD) patients. In contrast, Nucleoside Reverse Transcriptase Inhibitors (NRTIs) can act as P2RX7 antagonists and are drugs with an established safety record, including in children. We demonstrate here that AZT (Zidovudine) inhibits P2RX7 functions acting via the same allosteric site as other antagonists. Moreover, short-term AZT treatment at the peak of disease in DMD mdx mice attenuated the phenotype without any detectable side effects. Recovery was evident in the key parameters such as reduced sarcolemma permeability confirmed by lower serum creatine kinase levels and IgG influx into myofibres, decreased inflammatory cell numbers and inflammation markers in leg and heart muscles of treated mice. Moreover, this short-term therapy had some positive impact on muscle strength in vivo and no detrimental effect on mitochondria, which is the main side-effect of Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Given these results, we postulate that AZT could be quickly re-purposed for the treatment of this highly debilitating and lethal disease. This approach is not constrained by causative DMD mutations and may be effective in alleviating both muscle and non-muscle abnormalities.

A fixed-dose randomized controlled trial of olanzapine for psychosis in Parkinson disease

PubMed Central

Black, Kevin J

2013-01-01

Background: Psychosis is a common and debilitating side effect of long-term dopaminergic treatment of Parkinson disease (PD). While clozapine is an effective treatment, the need for blood monitoring has limited its first-line use.  Objective: Since olanzapine shows similar receptor affinity to clozapine, we hypothesized that it might be an effective alternative to clozapine for treatment of drug-induced psychosis (DIP) in PD, and that lower doses than usual might make it tolerable. Methods: In 1998-2003 we conducted a four-week, double-blind, placebo-controlled, parallel group, fixed-dose trial of olanzapine (0, 2.5mg, or 5mg) in 23 PD patients with DIP while allowing for clinically realistic dose adjustments of dopaminomimetic mid-study. The primary outcome measures were Brief Psychiatric Rating Scale (BPRS) ratings scored from videotaped interviews after study termination by an observer blinded to dose assignment and to interview timing, and CGI (Clinical Global Impression). The Unified Parkinson’s Disease Rating Scale motor subscale (UPDRS) was the primary measure of tolerability. Results: Intention-to-treat analysis found no significant differences among treatment groups in study completion or serious adverse events. However, a disproportionate number of olanzapine vs. placebo subjects reported mild side effects (p<0.04), many citing motor worsening. Fourteen patients completed the study (seven on placebo, two on 2.5mg olanzapine, five on 5mg olanzapine). In study completers, analysis by repeated measures ANOVA revealed no significant difference between olanzapine and placebo groups in BPRS psychosis reduction (p=0.536), parkinsonism (p=0.608), or any other measured parameters (CGI, MMSE, Beck Depression Inventory, Hamilton Depression score, PDQ‑39, Schwab-England ADL assessment, and sleep scores). Conclusion: This study adds to other evidence that olanzapine is ineffective in treating medication-induced psychosis in Parkinson disease. PMID:24627787

Telomeric repeat-binding factor 2: a marker for survival and anti-EGFR efficacy in oral carcinoma

PubMed Central

Raybaud, Hélène; Sudaka, Anne; Chamorey, Emmanuel; Brolih, Sanja; Monteverde, Martino; Merlano, Marco; Nigro, Cristiana Lo; Ambrosetti, Damien; Pagès, Gilles

2016-01-01

Oral Squamous Cell Carcinoma (OSCC) is the most common oral cancer worldwide. Treatments including surgery, radio- and chemo-therapies mostly result in debilitating side effects. Thus, a more accurate evaluation of patients at risk of recurrence after radio/chemo treatment is important for preserving their quality of life. We assessed whether the Telomeric Repeat-binding Factor 2 (TERF2) influences tumor aggressiveness and treatment response. TERF2 is over-expressed in many cancers but its correlation to patient outcome remains controversial in OSCC. Our retrospective study on sixty-two patients showed that TERF2 overexpression has a negative impact on survival time. TERF2-dependent survival time was independent of tumor size in a multivariate analysis. In vitro, TERF2 knockdown by RNA interference had no effect on cell proliferation, migration, senescence and apoptosis. Instead, TERF2 knockdown increased the expression of cytokines implicated in inflammation and angiogenesis, except for vascular endothelial growth factor. TERF2 knockdown resulted in a decrease vascularization and growth of xenograft tumors. Finally, response to erlotinib/Tarceva and cetuximab/Erbitux treatment was increased in TRF2 knocked-down cells. Hence, TERF2 may represent an independent marker of survival for OSCC and a predictive marker for cetuximab/Erbitux and erlotinib/Tarceva efficacy. PMID:27329590

MP-4 Contributes to Snake Venom Neutralization by Mucuna pruriens Seeds through an Indirect Antibody-mediated Mechanism*

PubMed Central

Kumar, Ashish; Gupta, Chitra; Salunke, Dinakar M.

2016-01-01

Mortality due to snakebite is a serious public health problem, and available therapeutics are known to induce debilitating side effects. Traditional medicine suggests that seeds of Mucuna pruriens can provide protection against the effects of snakebite. Our aim is to identify the protein(s) that may be important for snake venom neutralization and elucidate its mechanism of action. To this end, we have identified and purified a protein from M. pruriens, which we have named MP-4. The full-length polypeptide sequence of MP-4 was obtained through N-terminal sequencing of peptide fragments. Sequence analysis suggested that the protein may belong to the Kunitz-type protease inhibitor family and therefore may potentially neutralize the proteases present in snake venom. Using various structural and biochemical tools coupled with in vivo assays, we are able to show that MP-4 does not afford direct protection against snake venom because it is actually a poor inhibitor of serine proteases. Further experiments showed that antibodies generated against MP-4 cross-react with the whole venom and provide protection to mice against Echis carinatus snake venom. This study shows that the MP-4 contributes significantly to the snake venom neutralization activity of M. pruriens seeds through an indirect antibody-mediated mechanism. PMID:26987900

Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

PubMed Central

Ferenczy, Michael W.; Marshall, Leslie J.; Nelson, Christian D. S.; Atwood, Walter J.; Nath, Avindra; Khalili, Kamel

2012-01-01

Summary: Progressive multifocal leukoencephalopathy (PML) is a debilitating and frequently fatal central nervous system (CNS) demyelinating disease caused by JC virus (JCV), for which there is currently no effective treatment. Lytic infection of oligodendrocytes in the brain leads to their eventual destruction and progressive demyelination, resulting in multiple foci of lesions in the white matter of the brain. Before the mid-1980s, PML was a relatively rare disease, reported to occur primarily in those with underlying neoplastic conditions affecting immune function and, more rarely, in allograft recipients receiving immunosuppressive drugs. However, with the onset of the AIDS pandemic, the incidence of PML has increased dramatically. Approximately 3 to 5% of HIV-infected individuals will develop PML, which is classified as an AIDS-defining illness. In addition, the recent advent of humanized monoclonal antibody therapy for the treatment of autoimmune inflammatory diseases such as multiple sclerosis (MS) and Crohn's disease has also led to an increased risk of PML as a side effect of immunotherapy. Thus, the study of JCV and the elucidation of the underlying causes of PML are important and active areas of research that may lead to new insights into immune function and host antiviral defense, as well as to potential new therapies. PMID:22763635

Stereoscopic filming for investigating evasive side-stepping and anterior cruciate ligament injury risk

NASA Astrophysics Data System (ADS)

Lee, Marcus J. C.; Bourke, Paul; Alderson, Jacqueline A.; Lloyd, David G.; Lay, Brendan

2010-02-01

Non-contact anterior cruciate ligament (ACL) injuries are serious and debilitating, often resulting from the performance of evasive sides-stepping (Ssg) by team sport athletes. Previous laboratory based investigations of evasive Ssg have used generic visual stimuli to simulate realistic time and space constraints that athletes experience in the preparation and execution of the manoeuvre. However, the use of unrealistic visual stimuli to impose these constraints may not be accurately identifying the relationship between the perceptual demands and ACL loading during Ssg in actual game environments. We propose that stereoscopically filmed footage featuring sport specific opposing defender/s simulating a tackle on the viewer, when used as visual stimuli, could improve the ecological validity of laboratory based investigations of evasive Ssg. Due to the need for precision and not just the experience of viewing depth in these scenarios, a rigorous filming process built on key geometric considerations and equipment development to enable a separation of 6.5 cm between two commodity cameras had to be undertaken. Within safety limits, this could be an invaluable tool in enabling more accurate investigations of the associations between evasive Ssg and ACL injury risk.

Robot-Assisted Task-Specific Training in Cerebral Palsy

ERIC Educational Resources Information Center

Krebs, Hermano I.; Ladenheim, Barbara; Hippolyte, Christopher; Monterroso, Linda; Mast, Joelle

2009-01-01

Our goal was to examine the feasibility of applying therapeutic robotics to children and adults with severe to moderate impairment due to cerebral palsy (CP). Pilot results demonstrated significant gains for both groups. These results suggest that robot-mediated therapy may be an effective tool to ameliorate the debilitating effects of CP and…

Oxidative Stress: A Unifying Mechanism for Cell Damage Induced by Noise, (Water-Pipe) Smoking, and Emotional Stress-Therapeutic Strategies Targeting Redox Imbalance.

PubMed

Golbidi, Saeid; Li, Huige; Laher, Ismail

2018-03-20

Modern technologies have eased our lives but these conveniences can impact our lifestyles in destructive ways. Noise pollution, mental stresses, and smoking (as a stress-relieving solution) are some environmental hazards that affect our well-being and healthcare budgets. Scrutinizing their pathophysiology could lead to solutions to reduce their harmful effects. Recent Advances: Oxidative stress plays an important role in initiating local and systemic inflammation after noise pollution, mental stress, and smoking. Lipid peroxidation and release of lysolipid by-products, disturbance in activation and function of nuclear factor erythroid 2-related factor 2 (Nrf2), induction of stress hormones and their secondary effects on intracellular kinases, and dysregulation of intracellular Ca 2+ can all potentially trigger other vicious cycles. Recent clinical data suggest that boosting the antioxidant system through nonpharmacological measures, for example, lifestyle changes that include exercise have benefits that cannot easily be achieved with pharmacological interventions alone. Indiscriminate manipulation of the cellular redox network could lead to a new series of ailments. An ideal approach requires meticulous scrutiny of redox balance mechanisms for individual pathologies so as to create new treatment strategies that target key pathways while minimizing side effects. Extrapolating our understanding of redox balance to other debilitating conditions such as diabetes and the metabolic syndrome could potentially lead to devising a unifying therapeutic strategy. Antioxid. Redox Signal. 28, 741-759.

Acute migraine: Current treatment and emerging therapies

PubMed Central

Kalra, Arun A; Elliott, Debra

2007-01-01

Migraine is a common disabling primary headache disorder. Despite the need for a perfect treatment of this debilitating condition, the ideal “cure” eludes us. In 1992, the first triptan was released in the US for use in acute migraine. Triptans are more specific for the serotonin receptor 5-hydroxy triptamine (5-HT) 1 than previously prescribed drugs, such as ergotamines, with fewer side effects. This was an important first step in specific acute migraine therapy. Today however, triptans continue to be underutilized. There remains a concern, among practitioners and patients, about possible cardiovascular safety issues, despite the lack of strong evidence of serious adverse events. In fact, triptans now have a safe track record over more than a decade of use. Other perceived downfalls to use, include cost and variable efficacy. The more we learn about the clinical features and pathophysiology of migraine, the closer we are to finding a satisfactory monotherapy. Until then, recognizing that mixed mechanisms underlie migraine symptoms, rational polytherapy can be useful. Research on the roles of serotonin, calcitonin gene related peptide, glutamine and N-methyl-D-aspartate in the trigeminovascular system holds promise for those searching for the perfect migraine headache cure. PMID:18488069

Acute migraine: Current treatment and emerging therapies.

PubMed

Kalra, Arun A; Elliott, Debra

2007-06-01

Migraine is a common disabling primary headache disorder. Despite the need for a perfect treatment of this debilitating condition, the ideal "cure" eludes us. In 1992, the first triptan was released in the US for use in acute migraine. Triptans are more specific for the serotonin receptor 5-hydroxy triptamine (5-HT) 1 than previously prescribed drugs, such as ergotamines, with fewer side effects. This was an important first step in specific acute migraine therapy. Today however, triptans continue to be underutilized. There remains a concern, among practitioners and patients, about possible cardiovascular safety issues, despite the lack of strong evidence of serious adverse events. In fact, triptans now have a safe track record over more than a decade of use. Other perceived downfalls to use, include cost and variable efficacy. The more we learn about the clinical features and pathophysiology of migraine, the closer we are to finding a satisfactory monotherapy. Until then, recognizing that mixed mechanisms underlie migraine symptoms, rational polytherapy can be useful. Research on the roles of serotonin, calcitonin gene related peptide, glutamine and N-methyl-D-aspartate in the trigeminovascular system holds promise for those searching for the perfect migraine headache cure.

Nutrient Optimization Using Response Surface Methodology for Simultaneous Biomass and Bioactive Compound Production by Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes).

PubMed

Ofosu, Fred K; Yu, Xiaobin; Wang, Qiang; Li, Hanguang

2016-01-01

Due to the unpleasant side effects of long-term use of commercially available drugs, the discovery and development of natural therapeutic agents to prevent life-debilitating diseases is urgently needed. In the present study, the optimization of medium composition for maximum mycelial biomass and bioactive compounds production by Hericium erinaceus was studied using response surface methodology based on a central composite design. Under the optimal conditions and at a pH of 5.41 ± 0.28, the maximum mycelial biomass and exopolysaccharide production reached 25.0 ± 1.38 g/L and 1.73 ± 0.06 g/L, respectively, compared with 22.65 ± 0.10 g/L and 1.56 ± 0.23 g/L in the basal medium, after 7 days of cultivation. Furthermore, we report for the first time the production of adenosine, both intra- and extracellularly in submerged cultures of H. erinaceus. Although most of the adenosine detected existed in the culture medium, the highest intracellular and extracellular adenosine concentrations of 150.84 ± 1.87 mg/L and 142.48 ± 3.78 mg/L were achieved after 7 and 6 days of cultivation, respectively.

Portrait of an Illness.

ERIC Educational Resources Information Center

Ricci, Mary Lynne L.

1993-01-01

Author relates story of her own debilitation, survival, and ultimate rehabilitation from Systemic Lupus Erythematosus. Describes effects of disease process itself and of drug therapy that caused delusions and hallucinations. Traces how patient received art therapy through hospital occupational therapy department, describing her artwork and its…

Biomarkers and Brain Mechanisms of Gulf War Illness

DTIC Science & Technology

Gulf War illness (GWI), a chronic and debilitating pain, headaches, impaired memory and thinking, fatigue, respiratory and gastrointestinal symptoms...believed to be causative of the illness . The pathobiological mechanisms of GWI are unknown; there are no validated diagnostic tests, nor are there effective

Perceived Fear Appeals and Examination Performance: Facilitating or Debilitating Outcomes?

ERIC Educational Resources Information Center

Putwain, Dave; Symes, Wendy

2011-01-01

This study examines whether students' perception of classroom fear appeals concerning a forthcoming high-stakes examination are associated with facilitating or debilitating performance outcomes. Self-report data were collected for perceived fear appeals, test anxiety and achievement goals from a sample of 273 students in their final year of…

Photolytically driven generation of dissolved oxygen and increased oxyhemoglobin in whole blood.

PubMed

Monzyk, Bruce F; Burckle, Eric C; Carleton, Linda M; Busch, James; Dasse, Kurt A; Martin, Peter M; Gilbert, Richard J

2006-01-01

The severely debilitating nature of chronic lung disease has long provided the impetus for the development of technologies to supplement the respiratory capacity of the human lung. Although conventional artificial lung technologies function by delivering pressurized oxygen to the blood through a system of hollow fibers or tubes, our approach uses photolytic energy to generate dissolved oxygen (DO) from the water already present in blood, thus eliminating the need for gas delivery. We have previously demonstrated that it is feasible to generate dissolved oxygen from water based on UVA illumination of a highly absorbent TiO2 thin film. In the current study, we extend this work by using photolytic energy to generate DO from whole blood, thus resulting in an increase of oxyhemoglobin as a function of back side TiO2 surface film illumination. Initial experiments, performed with Locke's Ringer solution, demonstrated effective film thickness and material selection for the conductive layer. The application of a small bias voltage was used to conduct photogenerated electrons from the aqueous phase to minimize electron recombination with the DO.Mixed arterial-venous bovine blood was flowed in a recirculating loop over TiO2 nanocrystalline films illuminated on the side opposite the blood (or "back side") to eliminate the possibility of any direct exposure of blood to light. After light exposure of the TiO2 film, the fraction of oxyhemoglobin in the blood rapidly increased to near saturation and remained stable throughout the trial period. Last, we evaluated potential biofouling of the DO generating surface by scanning electron microscopy, after photolytically energized DO generation in whole blood, and observed no white or red blood cell surface deposition, nor the accumulation of any other material at this magnification. We conclude that it is feasible to photolytically oxygenate the hemoglobin contained in whole blood with oxygen derived from the blood's own water content without involving a gaseous phase.

Ketamine as a Rapid Treatment for Post-Traumatic Stress Disorder

DTIC Science & Technology

2011-10-01

Post - traumatic stress disorder ( PTSD ) is a debilitating anxiety disorder characterized by intrusive re-experiences of the traumatic events...08-1-0602 TITLE: Ketamine as a Rapid Treatment for Post - Traumatic Stress Disorder PRINCIPAL INVESTIGATOR: Dennis Charney...dissociative effects of ketamine but not have any sustained anxiolytic and antidepressant effects. Forty individuals diagnosed with post - traumatic

Auditory Working Memory Load Impairs Visual Ventral Stream Processing: Toward a Unified Model of Attentional Load

ERIC Educational Resources Information Center

Klemen, Jane; Buchel, Christian; Buhler, Mira; Menz, Mareike M.; Rose, Michael

2010-01-01

Attentional interference between tasks performed in parallel is known to have strong and often undesired effects. As yet, however, the mechanisms by which interference operates remain elusive. A better knowledge of these processes may facilitate our understanding of the effects of attention on human performance and the debilitating consequences…

Out-of-Class Anxiety in a Non-English Speaking Context and Its Effects on Intelligibility and Comprehensibility

ERIC Educational Resources Information Center

Wilang, Jeffrey Dawala; Singhasiri, Wareesiri

2017-01-01

Using Englishes as a lingua franca ("EsLF") or international language among EFL learners in an out-of-class setting induces anxiety, then debilitates the intelligibility and comprehensibility of speakers. This research project reports the conceptualisation of EsLF anxiety and its effects on intelligibility and comprehensibility, with the…

The Successful Treatment of Specific Phobia in a College Counseling Center

ERIC Educational Resources Information Center

Adler, Jonathan M.; Cook-Nobles, Robin

2011-01-01

Specific phobias are highly prevalent among college students and can be quite debilitating. However, students often do not present for treatment for phobias and, when they do, often do not receive effective treatment. This article will present a case study of the effective treatment of specific phobia using cognitive-behavioral therapy with an…

Lionfish envenomation.

PubMed

Kasdan, M L; Kasdan, A S; Hamilton, D L

1987-10-01

Correct and immediate care can significantly reduce the debilitating effects of Scorpaenidae evenomation. The lack of immediate heat application to the wound in our case report may have contributed to the complications and eventual loss of motion in the affected area, since the toxic ingredient, a nondialyzable protein, remained active.

Hispanic Americans: Their Future Is our Future.

ERIC Educational Resources Information Center

Howe, Christopher K.

1995-01-01

Discusses the importance of educating the growing Hispanic population in Catholic schools, highlighting such effects of the high drop-out rate as underemployment, poorer health, debilitated self-esteem, decreased political participation, and increased criminal behavior. Provides examples of techniques and programs that help keep Hispanic students…

Research protocol for a digital intervention to reduce stigma among males with a personal experience of suicide in the Australian farming community.

PubMed

Kennedy, Alison J; Versace, Vincent Lawrence; Brumby, Susan A

2016-11-29

Australian farming communities have up to twice the suicide rate of the general population. Men, particularly, demonstrate debilitating self- and perceived-stigma associated with an experience of suicide. The Ripple Effect is aimed to reduce suicide stigma within the social, cultural, geographical and psychological contexts in which it occurs. A mixed-method design with multi-level evaluation will be effected following the development and delivery of a personalised website experience (combining shared stories, education, personal goal setting and links to resources) to farming men, aged 30-64 years, with an experience of suicide. Pre- and post-surveys will be used to assess changes in self- and perceived-stigma and suicide literacy. Online feedback from participants and semi-structured interviews during follow-up will be thematically analysed. This project will provide information about increasingly accessible, innovative approaches to reducing the debilitating health and wellbeing effects of suicide stigma on a population of Australia's farmers. This research protocol was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN: ACTRN12616000289415 ) on 7 th March, 2016.

Crystal structure of the 28 kDa glutathione S-transferase from Schistosoma haematobium.

PubMed

Johnson, Kenneth A; Angelucci, Francesco; Bellelli, Andrea; Hervé, Maxime; Fontaine, Josette; Tsernoglou, Demetrious; Capron, André; Trottein, François; Brunori, Maurizio

2003-09-02

Schistomiasis is a debilitating parasitic disease which affects 200 million people, causing life-threatening complications in 10% of the patients. This paper reports the crystal structure of the Schistosoma haematobium 28 kDa glutathione S-transferase, a multifunctional enzyme involved in host-parasite interactions and presently considered as a promising vaccine candidate against schistosomiasis. The structures of the GSH-free enzyme, as well as the partially (approximately 40%) and almost fully (approximately 80%) GSH-saturated enzyme, exhibit a unique feature, absent in previous GST structures, concerning the crucial and invariant Tyr10 side chain which occupies two alternative positions. The canonical conformer, which allows an H-bond to be formed between the side chain hydroxyl group and the activated thiolate of GSH, is somewhat less than 50% occupied. The new conformer, with the phenoxyl ring on the opposite side of the mobile loop connecting strand 1 and helix 1, is stabilized by a polar interaction with the guanidinium group of the conserved Arg21 side chain. The presence of two conformers of Tyr10 may provide a clue about clarifying the multiple catalytic functions of Sh28GST and might prove to be relevant for the design of specific antischistosomal drugs. The K(d) for GSH binding was determined by equilibrium fluorescence titrations to be approximately 3 microM and by stopped-flow rapid mixing experiments to be approximately 9 microM. The relatively tight binding of GSH by Sh28GST explains the residually bound GSH in the crystal and supports a possible role of GSH as a tightly bound cofactor involved in the catalytic mechanism for prostaglandin D(2) synthase activity.

Morphine amplifies mechanical allodynia via TLR4 in a rat model of spinal cord injury

PubMed Central

Ellis, Amanda; Grace, Peter M.; Wieseler, Julie; Favret, Jacob; Springer, Kendra; Skarda, Bryce; Hutchinson, Mark R.; Falci, Scott; Rice, Kenner C.; Maier, Steven F.; Watkins, Linda R.

2016-01-01

Central neuropathic pain (CNP) is a pervasive, debilitating problem that impacts thousands of people living with central nervous system disorders, including spinal cord injury (SCI). Current therapies for treating this type of pain are ineffective and often have dose-limiting side effects. Although opioids are one of the most commonly used CNP treatments, recent animal literature has indicated that administering opioids shortly after a traumatic injury can actually have deleterious effects on long-term health and recovery. In order to study the deleterious effects of administering morphine shortly after trauma, we employed our low thoracic (T13) dorsal root avulsion model (Spinal Neuropathic Avulsion Pain, SNAP). Administering a weeklong course of 10 mg/kg/day morphine beginning 24 hr after SNAP resulted in amplified mechanical allodynia. Co-administering the non-opioid toll-like receptor 4 (TLR4) antagonist (+)-naltrexone throughout the morphine regimen prevented morphine-induced amplification of SNAP. Exploration of changes induced by early post-trauma morphine revealed that this elevated gene expression of TLR4, TNF, IL-1β, and NLRP3, as well as IL-1β protein at the site of spinal cord injury. These data suggest that a short course of morphine administered early after spinal trauma can exacerbate CNP in the long term. TLR4 initiates this phenomenon and, as such, may be potential therapeutic targets for preventing the deleterious effects of administering opioids after traumatic injury. PMID:27519154

Tart cherry supplementation improves working memory, hippocampal inflammation and autophagy in aged rats

USDA-ARS?s Scientific Manuscript database

High consumption of fruits and vegetables has been associated with reduced risk of debilitating diseases and improved cognition in aged populations. These beneficial effects have been attributed to the antioxidant/anti-inflammation properties of phytochemicals found in fruits and vegetables. Tart ch...

Menarche: Responses of Early Adolescent Females.

ERIC Educational Resources Information Center

McGrory, Arlene

1990-01-01

Investigated responses of menarcheal age females to menarche. Results from 95 girls indicated that premenarcheal girls thought menses was more debilitating than did postmenarcheal girls. Subjects who had been menstruating longer considered menses natural event but denied its effects. Found no significant difference in overall self-esteem and…

Isolated displaced non-union of a triquetral body fracture: a case report.

PubMed

Rasoli, Sonia; Ricks, Matthew; Packer, Greg

2012-02-10

Fractures of the body of the triquetral bone are the second most common carpal fractures, and these fractures can be missed on plain X-ray. Although non-union of triquetral body fractures is very rare, such cases are associated with considerable morbidity and reduction in functional activity. We report the case of a 29-year-old Caucasian British man who sustained an isolated displaced triquetral body fracture that resulted in non-union, who was treated surgically. We describe an original operative management for this debilitating injury. An open reduction and internal fixation using double headed compression screws was performed, without bone grafting, and with early immobilization of the wrist. We propose this novel approach and advocate early clinical suspicion of triquetral body fractures in patients with a history of fall on an outstretched hand and ulnar sided wrist pain. We recommend evaluation using computed tomography or magnetic resonance imaging scanning.

76 FR 78530 - Applications for Food and Drug Administration Approval To Market a New Drug; Revision of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-19

... applies to sole manufacturers of products that meet the following three criteria: 1. The products are life supporting, life sustaining, or intended for use in the prevention of a debilitating disease or condition; 2... drug is ``life supporting, life sustaining, or intended for use in the prevention of a debilitating...

Facilitating and Debilitating Test Anxiety Among College Students and Volunteers for Desensitization Workshops

ERIC Educational Resources Information Center

Hudesman, John; Wiesner, Ezra

1978-01-01

Examines whether the degree of facilitating and debilitating test anxiety is different for students who volunteer for test anxiety desensitization workshops than it is for the general college population, whether test anxiety in urban community college students is correlated, and whether either or both of the AAT scales are predictive of student…

The Effect of an Educator's Teaching Style on the Math Anxiety of Adult Learners

ERIC Educational Resources Information Center

Hosch, Mary L.

2014-01-01

Many adults are obstructed from specialized professions based on their anxiety of math. Math anxiety has been extensively researched for over 3 decades. Scholars have attempted to define its origins as well as the means to eliminate its often-debilitating effect on learners. Research indicates that learners with math anxiety often give up career…

Integrating diet and exercise into care of prostate cancer patients on androgen deprivation therapy

PubMed Central

Moyad, Mark A; Newton, Robert U; Tunn, Ulf W; Gruca, Damian

2016-01-01

Improved diagnosis and treatment regimens have resulted in greater longevity for men with prostate cancer. This has led to an increase in both androgen deprivation therapy (ADT) use and duration of exposure, and therefore to its associated adverse effects, such as sexual dysfunction, osteoporosis, reduced muscle mass, increased fat mass, and increased incidence of cardiovascular disease and type 2 diabetes. Given that the adverse effects of ADT are systemic, often debilitating, and difficult to treat, efforts continue in the development of new strategies for long-term management of prostate cancer. The PubMed database was searched to select trials, reviews, and meta-analyses in English using such search terms as “prostate cancer” and “androgen deprivation therapy”, “cardiovascular risk”, “lean body mass”, “exercise”, and “diet”. The initial searches produced 379 articles with dates 2005 or more recent. Articles published after 2004 were favored. This review utilizes the latest data to provide a status update on the effects of exercise and diet on patients with prostate cancer, focusing on ADT-associated side effects, and it discusses the evidence for such interventions. Since the evidence of large-scale trials in patients with prostate cancer is missing, and an extrapolation of supporting data to all patient subgroups cannot be provided, individualized risk assessments remain necessary before the initiation of exercise and diet programs. Exercise, diet, and nutritional supplementation interventions have the potential to provide effective, accessible, and relatively inexpensive strategies for mitigating ADT-associated toxicities without introducing additional adverse effects. PMID:27574584

3 CFR 8460 - Proclamation 8460 of December 2, 2009. Critical Infrastructure Protection Month, 2009

Code of Federal Regulations, 2010 CFR

2010-01-01

... the United States of America A Proclamation Critical infrastructure protection is an essential element... have a debilitating effect on security, national economic security, public health or safety. From water... country's essential resources are safe and capable of recovering from disruptive incidents. The Department...

Use of Transcranial Magnetic Stimulation in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Oberman, Lindsay M.; Rotenberg, Alexander; Pascual-Leone, Alvaro

2015-01-01

The clinical, social and financial burden of autism spectrum disorder (ASD) is staggering. We urgently need valid and reliable biomarkers for diagnosis and effective treatments targeting the often debilitating symptoms. Transcranial magnetic stimulation (TMS) is beginning to be used by a number of centers worldwide and may represent a novel…

Chemical Dependency, Denial, and the Academic Lifestyle.

ERIC Educational Resources Information Center

Donovan, Bruce E.

1990-01-01

The effects of problems with alcohol and other drugs are sometimes subtle, sometimes extravagant, and always debilitating. The tendency for individuals to deny their own problems makes the need for firm and compassionate colleagues more important. Intervention is a way of bringing sympathetic help to a colleague in distress. (MLW)

Learning to Live with Doubt: Kierkegaard, Freire, and Critical Pedagogy

ERIC Educational Resources Information Center

Roberts, Peter

2017-01-01

What role does doubt play in education? This article addresses this question, initially via an examination of Søren Kierkegaard's "Philosophical Fragments". Kierkegaard, through his pseudonym Johannes Climacus, draws attention to the potentially debilitating and destructive effects of doubt on both teachers and learners. The work of…

Understanding and Treating Social Phobia

ERIC Educational Resources Information Center

Curtis, Russell C.; Kimball, Amy; Stroup, Erin L.

2004-01-01

Social phobia, a relatively obscure disorder, is receiving increased attention due to evidence suggesting that it is more prevalent and debilitative than once thought. The purpose of this article is to help counselors better understand the nature of and treatments for this disorder. Effective behavioral and pharmacological approaches are reviewed,…

Use and abuse of opioid analgesics in chronic pain.

PubMed Central

Goldman, B.

1993-01-01

Primary care physicians are frequently required to treat patients with chronic debilitating pain. Opioid analgesics can successfully manage chronic pain. To prescribe opioid analgesics effectively, physicians must identify appropriate patients. Several methods can be used to identify and distinguish appropriate patients, addicted patients, and for-profit drug seekers. PMID:8097128

Comparative Effectiveness of Smoking Prevention Programs.

ERIC Educational Resources Information Center

Jason, Leonard A.; Mollica, Mark

Given the documented link between smoking and later debilitating health conditions, a need exists to investigate educational programs aimed at reducing rates of smoking among school-age children. An entire class of ninth graders was involved in a treatment condition featuring either role-playing and discussion or discussion only. While both…

Increasing the Effectiveness of Education for Students with Tourette Syndrome.

ERIC Educational Resources Information Center

Wilson, Jeni; Shrimpton, Bradley

This paper examines the educational implications for students with Tourette syndrome (TS) and outlines a multi-dimensional approach for improving their education. It presents data from two qualitative studies in Australia. TS is a debilitating neurological disorder that causes involuntary vocal and motor tics. The first study investigated the…

Nutritional interventions for the adjunctive treatment of schizophrenia: a brief review.

PubMed

Arroll, Megan Anne; Wilder, Lorraine; Neil, James

2014-09-16

Schizophrenia is a chronic condition that impacts significantly not only on the individual and family, but the disorder also has wider consequences for society in terms of significant costs to the economy. This highly prevalent condition affects approximately 1% of the worldwide population, yet there are few therapeutic options. The predominant treatment strategy for schizophrenia is anti-psychotic medication (with or without additional talking therapy) even though this approach lacks efficacy in managing the negative symptoms of the condition, is not effective in one-third of the patient group and the side effects of the medication can be severe and debilitating. In recent years, a number of pathophysiological processes have been identified in groups of people with schizophrenia including oxidative stress, one-carbon metabolism and immune-mediated responses. A number of studies have shown that these altered physiological mechanisms can be ameliorated by nutritional interventions in some individuals with schizophrenia. This review briefly describes the aforementioned processes and outlines research that has investigated the utility of nutritional approaches as an adjunct to anti-psychotic medication including antioxidant and vitamin B supplementation, neuroprotective and anti-inflammatory nutrients and exclusion diets. Whilst none of these interventions provides a 'one-size-fits-all' therapeutic solution, we suggest that a personalised approach warrants research attention as there is growing agreement that schizophrenia is a spectrum disorder that develops from the interplay between environmental and genetic factors.

Epigenetic targeting of histone deacetylase: therapeutic potential in Parkinson's disease?

PubMed

Harrison, Ian F; Dexter, David T

2013-10-01

Parkinson's disease (PD) is the most common movement disorder affecting more than 4million people worldwide. The primary motor symptoms of the disease are due to degeneration of dopaminergic nigrostriatal neurons. Dopamine replacement therapies have therefore revolutionised disease management by partially controlling these symptoms. However these drugs can produce debilitating side effects when used long term and do not protect degenerating neurons against death. Recent evidence has highlighted a pathological imbalance in PD between the acetylation and deacetylation of the histone proteins around which deoxyribonucleic acid (DNA) is coiled, in favour of excessive histone deacetylation. This mechanism of adding/removing acetyl groups to histone lysine residues is one of many epigenetic regulatory processes which control the expression of genes, many of which will be essential for neuronal survival. Hence, such epigenetic modifications may have a pathogenic role in PD. It has therefore been hypothesised that if this pathological imbalance can be corrected with the use of histone deacetylase inhibiting agents then neurodegeneration observed in PD can be ameliorated. This article will review the current literature with regard to epigenetic changes in PD and the use of histone deacetylase inhibitors (HDACIs) in PD: examining the evidence of the neuroprotective effects of numerous HDACIs in cellular and animal models of Parkinsonian cell death. Ultimately answering the question: does epigenetic targeting of histone deacetylases hold therapeutic potential in PD? Copyright © 2013 Elsevier Inc. All rights reserved.

Mitochondrial Agents for Bipolar Disorder.

PubMed

Pereira, Círia; Chavarria, Victor; Vian, João; Ashton, Melanie Maree; Berk, Michael; Marx, Wolfgang; Dean, Olivia May

2018-03-27

Bipolar disorder is a chronic and often debilitating illness. Current treatment options (both pharmaco- and psychotherapy) have shown efficacy, but for many leave a shortfall in recovery. Advances in the understanding of the pathophysiology of bipolar disorder suggest that interventions that target mitochondrial dysfunction may provide a therapeutic benefit. This review explores the current and growing theoretical rationale as well as existing preclinical and clinical data for those therapies aiming to target the mitochondrion in bipolar disorder. A Clinicaltrials.gov and ANZCTR search was conducted for complete and ongoing trials on mitochondrial agents used in psychiatric disorders. A PubMed search was also conducted for literature published between January 1981 and July 2017. Systematic reviews, randomized controlled trials, observational studies, case series, and animal studies with an emphasis on agents affecting mitochondrial function and its role in bipolar disorder were included. The search was augmented by manually searching the references of key papers and related literature. The results were presented as a narrative review. Mitochondrial agents offer new horizons in mood disorder treatment. While some negative effects have been reported, most compounds are overall well tolerated and have generally benign side-effect profiles. The study of neuroinflammation, neurodegeneration, and mitochondrial function has contributed the understanding of bipolar disorder's pathophysiology. Agents targeting these pathways could be a potential therapeutic strategy. Future directions include identification of novel candidate mitochondrial modulators as well as rigorous and well-powered clinical trials.

MP-4 Contributes to Snake Venom Neutralization by Mucuna pruriens Seeds through an Indirect Antibody-mediated Mechanism.

PubMed

Kumar, Ashish; Gupta, Chitra; Nair, Deepak T; Salunke, Dinakar M

2016-05-20

Mortality due to snakebite is a serious public health problem, and available therapeutics are known to induce debilitating side effects. Traditional medicine suggests that seeds of Mucuna pruriens can provide protection against the effects of snakebite. Our aim is to identify the protein(s) that may be important for snake venom neutralization and elucidate its mechanism of action. To this end, we have identified and purified a protein from M. pruriens, which we have named MP-4. The full-length polypeptide sequence of MP-4 was obtained through N-terminal sequencing of peptide fragments. Sequence analysis suggested that the protein may belong to the Kunitz-type protease inhibitor family and therefore may potentially neutralize the proteases present in snake venom. Using various structural and biochemical tools coupled with in vivo assays, we are able to show that MP-4 does not afford direct protection against snake venom because it is actually a poor inhibitor of serine proteases. Further experiments showed that antibodies generated against MP-4 cross-react with the whole venom and provide protection to mice against Echis carinatus snake venom. This study shows that the MP-4 contributes significantly to the snake venom neutralization activity of M. pruriens seeds through an indirect antibody-mediated mechanism. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Prevention of paclitaxel-induced peripheral neuropathy by lithium pretreatment

PubMed Central

Mo, Michelle; Erdelyi, Ildiko; Szigeti-Buck, Klara; Benbow, Jennifer H.; Ehrlich, Barbara E.

2012-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect that occurs in many patients undergoing chemotherapy. It is often irreversible and frequently leads to early termination of treatment. In this study, we have identified two compounds, lithium and ibudilast, that when administered as a single prophylactic injection prior to paclitaxel treatment, prevent the development of CIPN in mice at the sensory-motor and cellular level. The prevention of neuropathy was not observed in paclitaxel-treated mice that were only prophylactically treated with a vehicle injection. The coadministration of lithium with paclitaxel also allows for administration of higher doses of paclitaxel (survival increases by 60%), protects against paclitaxel-induced cardiac abnormalities, and, notably, does not interfere with the antitumor effects of paclitaxel. Moreover, we have determined a mechanism by which CIPN develops and have discovered that lithium and ibudilast inhibit development of peripheral neuropathy by disrupting the interaction between paclitaxel, neuronal calcium sensor 1 (NCS-1), and the inositol 1,4,5-trisphosphate receptor (InsP3R) to prevent treatment-induced decreases in intracellular calcium signaling. This study shows that lithium and ibudilast are candidate therapeutics for the prevention of paclitaxel-induced neuropathy and could enable patients to tolerate more aggressive treatment regimens.—Mo, M., Erdelyi, I., Szigeti-Buck, K., Benbow, J. H., Ehrlich, B. E. Prevention of paclitaxel-induced peripheral neuropathy by lithium pretreatment. PMID:22889832

Brain Stimulation in the Treatment of Chronic Neuropathic and Non-Cancerous Pain

PubMed Central

Plow, EB; Pascual-Leone, A; Machado, A

2012-01-01

Chronic neuropathic pain is one of the most prevalent and debilitating disorders. Conventional medical management, however, remains frustrating for both patients and clinicians owing to poor specificity of pharmacotherapy, delayed-onset of analgesia and extensive side-effects. Neuromodulation presents as a promising alternative, or at least an adjunct, as it is more specific in inducing analgesia without associated risks of pharmacotherapy. Here, we discuss common clinical and investigational methods of neuromodulation. Compared to clinical spinal cord stimulation (SCS), investigational techniques of cerebral neuromodulation, both invasive [deep brain stimulation (DBS) and motor cortical stimulation (MCS)] and noninvasive [repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS)], may be more advantageous. By adaptively targeting the multi-dimensional experience of pain, subtended by integrative pain circuitry in the brain, including somatosensory and thalamocortical, limbic and cognitive, cerebral methods may modulate the sensory-discriminative, affective-emotional and evaluative-cognitive spheres of the pain neuromatrix. Despite promise, the current state of results alludes to the possibility that cerebral neuromodulation has thus far not been effective in producing analgesia as intended in patients with chronic pain disorders. These techniques, thus, remain investigational and off-label. We discuss issues implicated in inadequate efficacy, variability of responsiveness and poor retention of benefit, while recommending design and conceptual refinements for future trials of cerebral neuromodulation in management of chronic neuropathic pain. PMID:22484179

Potentiation of latent inhibition by haloperidol and clozapine is attenuated in Dopamine D2 receptor (Drd-2)-deficient mice: Do antipsychotics influence learning to ignore irrelevant stimuli via both Drd-2 and non-Drd-2 mechanisms?

PubMed Central

O’Callaghan, Matthew J; Bay-Richter, Cecilie; O’Tuathaigh, Colm MP; Heery, David M; Waddington, John L; Moran, Paula M

2014-01-01

Whether the dopamine Drd-2 receptor is necessary for the behavioural action of antipsychotic drugs is an important question, as Drd-2 antagonism is responsible for their debilitating motor side effects. Using Drd-2 null mice (Drd2 -/-) it has previously been shown that Drd-2 is not necessary for antipsychotic drugs to reverse D-amphetamine disruption of latent inhibition (LI), a behavioural measure of learning to ignore irrelevant stimuli. Weiner’s ‘two-headed’ model indicates that antipsychotics not only reverse LI disruption, ‘disrupted LI’, but also potentiate LI when low/absent in controls, ‘persistent’ LI. We investigated whether antipsychotic drugs haloperidol or clozapine potentiated LI in wild-type controls or Drd2 -/-. Both drugs potentiated LI in wild-type but not in Drd2-/- mice, suggesting moderation of this effect of antipsychotics in the absence of Drd-2. Haloperidol potentiated LI similarly in both Drd1-/- and wild-type mice, indicating no such moderation in Drd1-/-. These data suggest that antipsychotic drugs can have either Drd-2 or non-Drd-2 effects on learning to ignore irrelevant stimuli, depending on how the abnormality is produced. Identification of the non-Drd-2 mechanism may help to identify novel non-Drd2 based therapeutic strategies for psychosis. PMID:25122042

Personal, interpersonal, and situational influences on behavioral self-handicapping.

PubMed

Brown, Christina M; Kimble, Charles E

2009-12-01

This study explored the combined effects of personal factors (participant sex), interpersonal factors (experimenter sex), and situational factors (performance feedback) on two forms of behavioral self-handicapping. Participants received non-contingent success or failure feedback concerning their performance on a novel ability and were given the opportunity to self-handicap before performing again. Behavioral self-handicapping took the form of (a) exerting less practice effort (practice) or (b) choosing a performance-debilitating tape (choice). Men practiced least after failure feedback and chose a debilitating tape if they were interacting with a female experimenter. Generally, across all participants in both choice and practice conditions, high performance concern and the presence of a male experimenter led to the most self-handicapping. Results are interpreted in terms of self-presentational concerns that emphasize a desire to impress or an awareness of the female or male experimenter's acceptance of self-handicappers.

Afghanistan: Nation or Narco State

DTIC Science & Technology

2007-06-01

Frontier Province in what is today Pakistan, home to the Pashtun tribes. Having become conscious of the debilitating effects of narcotics to both the...famous for aspirin, came up with a name for the awe-inspiringly powerful painkiller based on the German word heroisch, meaning heroic. It would...opiates as folk medicine and recreational euphoric during the last millennium raises some doubts about the possibility of effecting its eradication

'I feel stronger and younger all the time'-perspectives of elderly kidney transplant recipients: thematic synthesis of qualitative research.

PubMed

Pinter, Jule; Hanson, Camilla S; Craig, Jonathan C; Chapman, Jeremy R; Budde, Klemens; Halleck, Fabian; Tong, Allison

2016-09-01

Kidney transplantation offers improved survival and quality of life to an increasing number of elderly patients with end-stage kidney disease. However, elderly kidney transplant recipients may face unique challenges due to a higher burden of comorbidity, greater cumulative risk of immunosuppression-related complications and increasing frailty. We aimed to describe the perspectives of elderly kidney transplant recipients. Electronic databases were searched to April 2015. Qualitative studies were eligible if they reported views from elderly kidney transplant recipients (≥60 years). Thematic synthesis was used to analyse the findings. Twenty-one studies involving >116 recipients were included. We identified seven themes. 'Regaining strength and vitality' meant valuing the physical and psychosocial improvements in daily functioning and life participation. 'Extending life' was the willingness to accept any organ, including extended criteria kidneys, to prolong survival. 'Debt of gratitude' entailed conscious appreciation toward their donor while knowing they were unable to repay their sacrifice. 'Moral responsibility to maintain health' motivated adherence to medication and lifestyle recommendations out of an ethical duty to protect their gift for graft survival. 'Unabating and worsening forgetfulness' hindered self-management. 'Disillusionment with side effects and complications' reflected disappointment and exasperation with the unintended consequences of medications. 'Finality of treatment option' was an acute awareness that the current transplant may be their last. Kidney transplantation was perceived to slow and even reverse the experience of aging among elderly recipients, especially compared with dialysis. However, some were frustrated over persistent limitations after transplant, struggled with the burden of medication side effects and worried about a possible return to dialysis if the transplant failed. Clarifying patient expectations of transplantation, providing support to alleviate the debilitating impacts of immunosuppression and addressing fears about deteriorating health and graft failure may improve satisfaction and outcomes in elderly kidney transplant recipients. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Developing Gene Silencing for the Study and Treatment of Dystonia

DTIC Science & Technology

2015-11-01

cause abnormal twisting postures. DYT1 dystonia is an autosomal dominant disease with onset of dystonia during childhood . The most common early onset...SUPPLEMENTARY NOTES 14. ABSTRACT Dystonia is a debilitating neurological disease with no cure. In dystonia, there are involuntary muscle contractions that...is a debilitating neurological disease with no cure that is characterized by involuntary muscle contractions that cause abnormal twisting postures

Monoclonal Antibodies Passively Protect BALB/c Mice Against Burkholderia mallei Aerosol Challenge

DTIC Science & Technology

2006-03-01

November 2005 Glanders is a debilitating disease with no vaccine available. Murine monoclonal antibodies were produced against Burkholderia mallei , the... Glanders is a debilitating disease with no vaccine available. Murine monoclonal antibodies were produced against Burkholderia mallei , the etiologic... Burkholderia mallei auxotroph protects against aerosol-initiated glanders in mice. Vaccine 23:1986–1992. 17. Vyshelesskii, S. N. 1974. Glanders (Equinia). Tr

Adding smartphone-based cognitive-behavior therapy to pharmacotherapy for major depression (FLATT project): study protocol for a randomized controlled trial.

PubMed

Watanabe, Norio; Horikoshi, Masaru; Yamada, Mitsuhiko; Shimodera, Shinji; Akechi, Tatsuo; Miki, Kazuhira; Inagaki, Masatoshi; Yonemoto, Naohiro; Imai, Hissei; Tajika, Aran; Ogawa, Yusuke; Takeshima, Nozomi; Hayasaka, Yu; Furukawa, Toshi A

2015-07-07

Major depression is one of the most debilitating diseases in terms of quality of life. Less than half of patients suffering from depression can achieve remission after adequate antidepressant treatment. Another promising treatment option is cognitive-behavior therapy (CBT). However, the need for experienced therapists and substantive dedicated time prevent CBT from being widely disseminated. In the present study, we aim to examine the effectiveness of switching antidepressants and starting a smartphone-based CBT program at the same time, in comparison to switching antidepressants only, among patients still suffering from depression after adequate antidepressant treatment. A multi-center randomized trial is currently being conducted since September 2014. The smartphone-based CBT program, named the "Kokoro-App," for major depression has been developed and its feasibility has been confirmed in a previous open study. The program consists of an introduction, 6 sessions and an epilogue, and is expected to be completed within 9 weeks by patients. In the present trial, 164 patients with DSM-5 major depressive disorder and still suffering from depressive symptoms after adequate antidepressant treatment for more than 4 weeks will be allocated to the Kokoro-App plus switching antidepressant group or the switching antidepressant alone group. The participants allocated to the latter group will receive full components of the Kokoro-App after 9 weeks. The primary outcome is the change in the total score on the Patient Health Questionnaire through the 9 weeks of the program, as assessed at week 0, 1, 5 and 9 via telephone by blinded raters. The secondary outcomes include the change in the total score of the Beck Depression Inventory-II, change in side effects as assessed by the Frequency, Intensity and Burden of Side Effects Rating, and treatment satisfaction. An effective and reachable intervention may not only lead to healthier mental status among depressed patients, but also to reduced social burden from this illness. This paper outlines the background and methods of a trial that evaluates the possible additive value of a smartphone-based CBT program for treatment-resistant depression. UMIN-CTR: UMIN000013693 (registered on 1 June 2014).

A pilot randomised double blind controlled trial of the efficacy of purified fatty acids for the treatment of women with endometriosis-associated pain (PurFECT): study protocol.

PubMed

Abokhrais, Ibtisam M; Saunders, Philippa T K; Denison, Fiona C; Doust, Ann; Williams, Linda; Horne, Andrew W

2018-01-01

Endometriosis affects 6-10% of women and is associated with debilitating pelvic pain. It costs the UK > £2.8 billion per year in loss of productivity. Endometriosis can be managed by surgical excision or medically by ovarian suppression. However, ~ 75% symptoms recur after surgery and available medical treatments have undesirable side effects and are contraceptive. Omega-3 purified fatty acids (PUFA) have been shown in animal models to reduce factors that are thought to lead to endometriosis-associated pain, have minimal side effects, and no effects on fertility. This paper presents a protocol for a two-arm, pilot parallel randomised controlled trial (RCT) which aims to inform the planning of a future multicentre trial to evaluate the efficacy of Omega-3 PUFA in the management of endometriosis-associated pain in women. The study will recruit women with endometriosis over a 12-month period in the National Health Service (NHS) Lothian, UK, and randomise them to 8 weeks of treatment with Omega-3 PUFA or comparator (olive oil). The primary objective is to assess recruitment and retention rates. The secondary objectives are to determine the effectiveness/acceptability to participants of the proposed methods of recruitment/randomisation/treatments/questionnaires, to inform the sample size calculation and to refine the research methodology for a future large randomised controlled trial. Response to treatment will be monitored by pain scores and questionnaires assessing physical and emotional function compared at baseline and 8 weeks. We recognise that there may be potential difficulties in mounting a large randomised controlled trial for endometriosis to assess Omega-3 PUFA because they are a dietary supplement readily available over the counter and already used by women with endometriosis. We have therefore designed this pilot study to assess practical feasibility and following the 'Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials' recommendations for the design of chronic pain trials. ISRCTN44202346.

Thriving on Stress for Success. Principals Taking Action Series.

ERIC Educational Resources Information Center

Gmelch, Walter H.; Chan, Wilbert

When properly managed, stress can serve as a key to successful job performance. This book explores the link between pressure and performance in schools. It shows how to recognize stress as both a facilitator and debilitator of effective performance. Chapter 1 serves as a personal stress checkup. Chapter 2 explores the myths of administrative…

Determining the Debilitative Impact of Test Anxiety.

ERIC Educational Resources Information Center

Madsen, Harold S.

The detrimental effects of anxiety in English as a second language/foreign language (ESL/FL) are investigated. Although empirical research on the subject of ESL/FL test affect is limited, helpful insights on test anxiety exist in the psychological literature. Two constructs in the anxiety literature are considered relevant for this study: trait…

3 CFR 8494 - Proclamation 8494 of April 8, 2010. National D.A.R.E. Day, 2010

Code of Federal Regulations, 2011 CFR

2011-01-01

... substance abuse. Drug dependence affects individuals from all backgrounds, and its debilitating effects... to chemical inhalants, many substances can be harmful if abused, and preventing our children from... drug use with the young people in their lives. Community-based prevention and treatment programs can...

Two Self-Control Procedures in the Reduction of Targeted and Nontargeted Anxieties.

ERIC Educational Resources Information Center

Deffenbacher, Jerry L.; And Others

1979-01-01

Compared effects of relaxation as self-control and a self-control variant of systematic desensitization in reducing targeted (test anxiety) and nontargeted anxieties with those of wait-list and no-treatment expectancy controls. Groups given relaxation as self-control and modified desensitization reported less debilitating test anxiety than…

75 FR 52294 - Effective Date of Requirement for Premarket Approval for Four Class III Preamendments Devices

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-25

... Federal Food, Drug, and Cosmetic Act (the act), as amended by the Medical Device Amendments of 1976 (the... could lead to potentially debilitating or fatal thromboembolism. b. Excessive hemolysis--poor design of the hemodynamic characteristics of the device can lead to excess hemolysis. c. Inability to support...

Supporting Assessment Stress in Key Stage 4 Students

ERIC Educational Resources Information Center

Putwain, David William

2008-01-01

Research has indicated that 13% of students in the UK experience a high degree of assessment-related stress/anxiety, which may have debilitating health, emotional and educational effects. Recent policy initiatives have attempted to encourage a responsibility for promoting well-being in schools; however, at present there is little known about what,…

Assessment of Seizures and Related Symptomatology in Persons with Mental Retardation

ERIC Educational Resources Information Center

Mayville, Erik A.; Matson, Johnny L.

2004-01-01

Seizures can be debilitating across a number of physical, social, occupational, and personal variables. Given the deficits in all of these areas frequently present in persons with mental retardation, effective assessment and subsequent treatment of seizures is a primary goal for individuals with both mental retardation and epilepsy. To thoroughly…

Pen Pals without Borders: A Cultural Exchange of Teaching and Learning

ERIC Educational Resources Information Center

McMillon, Gwendolyn Michele Thompson

2009-01-01

When teachers and students are from different cultures, dissonance can occur in classrooms, which can be debilitating for effective literacy teaching and learning. Researchers have conducted studies in urban schools for many years, but the problem of cultural dissonance continues to plague many classrooms. It is imperative that teacher education…

High negative pressure subcutaneous suction drain for managing debilitating subcutaneous emphysema secondary to tube thoracostomy for an iatrogenic post computed tomography guided transthoracic needle biopsy pneumothorax: Case report and review of literature.

PubMed

Ahmed, Zeeshan; Patel, Pinakin; Singh, Suresh; Sharma, Raj Govind; Somani, Pankaj; Gouri, Abdul Rauf; Singh, Shiv

2016-01-01

Subcutaneous emphysema is a common complication of tube thoracostomy. Though self-limiting, it should be treated when it causes palpebral closure, dyspnea, dysphagia or undue disfigurement resulting in anxiety and distress to the patient. A 72year old man who was a known case of COPD on bronchodilators developed a large pneumothorax and respiratory distress after a CT guided transthoracic lung biopsy done for a lung opacity (approx. 3×3cm) at the right hilar region on Chest X-ray. Within 24h of an urgent tube thoracostomy, patient developed intractable subcutaneous emphysema with closure of palpebral fissure and dyspnea unresponsive to increasing suction on chest tube. A subcutaneous fenestrated drain was placed mid-way between the nipple and clavicle in the mid-clavicular line bilaterally. Continuous negative suction (-150mmHg) resulted in immediate, sustained relief and complete resolution within 5days. Extensive and debilitating SE (subcutaneous emphysema) has to be treated promptly to relieve patient discomfort, dysphagia or imminent respiratory compromise. A variety of treatment have been tried including infraclavicular blow-hole incisions, subcutaneous drains +/- negative pressure suction, fenestrated angiocatheters, Vacuum assisted dressings and increasing suction on a pre-existing chest tube. We describe a high negative pressure subcutaneous suction drain which provides immediate and sustained relief in debilitating SE. Debilitating subcutaneous emphysema which causes distress, anxiety, palpebral closure, dyspnoea or dysphagia requires intervention. High negative pressure subcutaneous suction drain provides immediate and sustained relief in extensive and debilitating SE. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Is GERD a Factor in Osteonecrosis of the Jaw? Evidence of Pathology Linked to G6PD Deficiency and Sulfomucins

PubMed Central

Swanson, Nancy L.; Li, Chen

2016-01-01

Osteonecrosis of the jaw (ONJ), a rare side effect of bisphosphonate therapy, is a debilitating disorder with a poorly understood etiology. FDA's Adverse Event Reporting System (FAERS) provides the opportunity to investigate this disease. Our goals were to analyze FAERS data to discover possible relationships between ONJ and specific conditions and drugs and then to consult the scientific literature to deduce biological explanations. Our methodology revealed a very strong association between gastroesophageal reflux and bisphosphonate-induced ONJ, suggesting acidosis as a key factor. Overgrowth of acidophilic species, particularly Streptococcus mutans, in the oral microbiome in the context of insufficient acid buffering due to impaired salivary glands maintains the low pH that sustains damage to the mucosa. Significant associations between ONJ and adrenal insufficiency, vitamin C deficiency, and Sjögren's syndrome were found. Glucose 6 phosphate dehydrogenase (G6PD) deficiency can explain much of the pathology. An inability to maintain vitamin C and other antioxidants in the reduced form leads to vascular oxidative damage and impaired adrenal function. Thus, pathogen-induced acidosis, hypoxia, and insufficient antioxidant defenses together induce ONJ. G6PD deficiency and adrenal insufficiency are underlying factors. Impaired supply of adrenal-derived sulfated sterols such as DHEA sulfate may drive the disease process. PMID:27773962

Epilepsy as a Network Disorder (2): What can we learn from other network disorders such as dementia and schizophrenia, and what are the implications for translational research?

PubMed

Scharfman, Helen E; Kanner, Andres M; Friedman, Alon; Blümcke, Ingmar; Crocker, Candice E; Cendes, Fernando; Diaz-Arrastia, Ramon; Förstl, Hans; Fenton, André A; Grace, Anthony A; Palop, Jorge; Morrison, Jason; Nehlig, Astrid; Prasad, Asuri; Wilcox, Karen S; Jette, Nathalie; Pohlmann-Eden, Bernd

2018-01-01

There is common agreement that many disorders of the central nervous system are 'complex', that is, there are many potential factors that influence the development of the disease, underlying mechanisms, and successful treatment. Most of these disorders, unfortunately, have no cure at the present time, and therapeutic strategies often have debilitating side effects. Interestingly, some of the 'complexities' of one disorder are found in another, and the similarities are often network defects. It seems likely that more discussions of these commonalities could advance our understanding and, therefore, have clinical implications or translational impact. With this in mind, the Fourth International Halifax Epilepsy Conference and Retreat was held as described in the prior paper, and this companion paper focuses on the second half of the meeting. Leaders in various subspecialties of epilepsy research were asked to address aging and dementia or psychosis in people with epilepsy (PWE). Commonalities between autism, depression, aging and dementia, psychosis, and epilepsy were the focus of the presentations and discussion. In the last session, additional experts commented on new conceptualization of translational epilepsy research efforts. Here, the presentations are reviewed, and salient points are highlighted. Copyright © 2017 Elsevier Inc. All rights reserved.

Cartilage Dysfunction in ALS Patients as Side Effect of Motion Loss: 3D Mechano-Electrochemical Computational Model

PubMed Central

Gaffney, Eamonn A.; Doblaré, Manuel

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease characterized by progressive weakness, muscle atrophy, and fasciculation. This fact results in a continuous degeneration and dysfunction of articular soft tissues. Specifically, cartilage is an avascular and nonneural connective tissue that allows smooth motion in diarthrodial joints. Due to the avascular nature of cartilage tissue, cells nutrition and by-product exchange are intermittently occurring during joint motions. Reduced mobility results in a change of proteoglycan density, osmotic pressure, and permeability of the tissue. This work aims to demonstrate the abnormal cartilage deformation in progressive immobilized articular cartilage for ALS patients. For this aim a novel 3D mechano-electrochemical model based on the triphasic theory for charged hydrated soft tissues is developed. ALS patient parameters such as tissue porosity, osmotic coefficient, and fixed anions were incorporated. Considering different mobility reduction of each phase of the disease, results predicted the degree of tissue degeneration and the reduction of its capacity for deformation. The present model can be a useful tool to predict the evolution of joints in ALS patients and the necessity of including specific cartilage protectors, drugs, or maintenance physical activities as part of the symptomatic treatment in amyotrophic lateral sclerosis. PMID:24991537

Effects of Streptococcus thermophilus TH-4 in a rat model of doxorubicin-induced mucositis.

PubMed

Wang, Hanru; Brook, Caitlin L; Whittaker, Alexandra L; Lawrence, Andrew; Yazbeck, Roger; Howarth, Gordon S

2013-08-01

Mucositis is a debilitating intestinal side effect of chemotherapeutic regimens. Probiotics have been considered a possible preventative treatment for mucositis. Streptococcus thermophilus TH-4 (TH-4), a newly identified probiotic, has been shown to partially alleviate mucositis induced by administration of the antimetabolite chemotherapy drug, methotrexate in rats; likely mediated through a mechanism of folate production. However, its effects against other classes of chemotherapy drug have yet to be determined. The authors investigated the effects of TH-4 in a rat model of mucositis induced by the anthracycline chemotherapy drug, doxorubicin. Gastrointestinal damage was induced in female Dark Agouti rats (148.3 ± 1.5 g) by intraperitoneal injection of doxorubicin (20 mg/kg). Animals recieved a daily oral gavage of TH-4 at 10(9) cfu/ml or skim milk (vehicle) from days 0 to 8. At day 6, rats were injected with either saline or doxorubicin. At kill, small intestinal tissues were collected for determination of sucrase and myeloperoxidase (MPO) activities and histological assessment. Body weight was significantly decreased by doxorubicin compared with normal controls (p < 0.05). Histological parameters, such as crypt depth and villus height, were also significantly decreased by doxorubicin. TH-4 partially prevented the loss of body weight induced by doxorubicin (2.3% compared with 4%), but provided no further therapeutic benefit. The minimal amelioration of doxorubicin-induced mucositis by TH-4 further supports folate production as a likely mechanism of TH-4 action against methotrexate-induced mucositis. Further studies into TH-4 are required to confirm its applicability to other conventional chemotherapy regimens.

Nefopam, a non-opioid analgesic, does not alleviate experimental work/effort dyspnoea in healthy humans: A randomised controlled trial.

PubMed

Dangers, Laurence; Laviolette, Louis; Charbit, Bény; Similowski, Thomas; Morélot-Panzini, Capucine

2016-08-01

Dyspnoea is a distressing and debilitating symptom with a major impact on quality of life. Alleviation of dyspnoea therefore constitutes a major clinical challenge. When causative physiological disorders cannot be corrected ("persistent dyspnoea"), nonspecific treatment must be considered. Morphine alleviates dyspnoea but has numerous side-effects including ventilatory depression, which justifies looking for alternatives. Certain forms of dyspnoea involve C-fibres, and can be attenuated by C-fibres blockade. We hypothesised that nefopam, a non-sedative benzoxazocine analgesic known to block the transient receptor potential vanilloid subtype 1 abundantly present on C-fibres, would attenuate dyspnoea. We conducted a randomised, double-blind, placebo-controlled crossover study of nefopam in healthy subjects submitted to experimental work/effort dyspnoea by inspiratory threshold loading (15 healthy male volunteers; age 23-41). We studied a perceptual outcome (dyspnoea visual analogue scale -D-VAS-) and a neurophysiological outcome (effect of nefopam on dyspnoea-pain counter-irritation as assessed by laser-evoked potentials; an effect of nefopam on dyspnoea was hypothetised to reduce the ability of dyspnoea to inhibit pain). Somaesthetic evoked potentials (SEPs) were studied as a control. A statistically significant decrease in LEP amplitude was observed in response to loading with nefopam (F = 19.1; p < 0.001) and placebo (F = 5.73 and p < 0.001), with no significant difference between nefopam and placebo and no change in SEP characteristics. In this study, nefopam did not exhibit any effects on dyspnoea. Copyright © 2016 Elsevier Ltd. All rights reserved.

New frontiers in mucositis.

PubMed

Peterson, Douglas E; Keefe, Dorothy M; Sonis, Stephen T

2012-01-01

Mucositis is among the most debilitating side effects of radiotherapy, chemotherapy, and targeted anticancer therapy. Research continues to escalate regarding key issues such as etiopathology, incidence and severity across different mucosae, relationships between mucosal and nonmucosal toxicities, and risk factors. This approach is being translated into enhanced management strategies. Recent technology advances provide an important foundation for this continuum. For example, evolution of applied genomics is fostering development of new algorithms to rapidly screen genomewide single-nucleotide polymorphisms (SNPs) for patient-associated risk prediction. This modeling will permit individual tailoring of the most effective, least toxic treatment in the future. The evolution of novel cancer therapeutics is changing the mucositis toxicity profile. These agents can be associated with unique mechanisms of mucosal damage. Additional research is needed to optimally manage toxicity caused by agents such as mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors, without reducing antitumor effect. There has similarly been heightened attention across the health professions regarding clinical practice guidelines for mucositis management in the years following the first published guidelines in 2004. New opportunities exist to more effectively interface this collective guideline portfolio by capitalizing upon novel technologies such as an Internet-based Wiki platform. Substantive progress thus continues across many domains associated with mucosal injury in oncology patients. In addition to enhancing oncology patient care, these advances are being integrated into high-impact educational and scientific venues including the National Cancer Institute Physician Data Query (PDQ) portfolio as well as a new Gordon Research Conference on mucosal health and disease scheduled for June 2013.

Spontaneous and deliberate dissociative states in military personnel: are such states helpful?

PubMed

Morgan, Charles A; Taylor, Marcus K

2013-08-01

This study explored distinctions between spontaneous and deliberate dissociative states in 335 military personnel exposed to stressful survival training. Participants completed the Clinician-Administered Dissociative States Scale (CADSS) after a stressful mock-captivity event. They were also asked to indicate whether the dissociative experiences just happened (i.e., spontaneous), or whether they chose to have them happen (i.e., deliberate); and whether they appraised the dissociative experience as helpful (i.e., facilitative) or hurtful (i.e., debilitative) to their ability to cope with the stressful event. A majority (95.4%) endorsed dissociative states during stress. More than half (57.4%) described dissociative experiences as spontaneous, 13.0% as deliberate, and 29.5% endorsed neither. In Special Forces soldiers only, those who endorsed facilitative dissociation exhibited higher total CADSS scores than those who endorsed debilitative dissociation. Seventy-three percent of spontaneous dissociators described the experience as debilitative to coping with stress; conversely, 76% of deliberate dissociators said these experiences facilitated coping with stress. Individuals with prior trauma exposure tended to appraise dissociative states as more debilitative to coping. This research may enhance the fidelity of studies of dissociation constructs and may offer pivot points for prevention and treatment of stress-related disorders. Published 2013. This article is a US Government work and is in the public domain in the USA.

Compassion Fatigue in the Military Caregiver

DTIC Science & Technology

2009-03-01

Compassion Fatigue/ Burnout Syndrome Figley, C (1995; 97)19 Sprang, Clark, and Whitt-Woosley in their article, “Compassion Fatigue, Compassion...alternative or additional programs, process or intervention to address compassion fatigue, burnout , stress disorder or other debilitating post-traumatic...effects. 15. SUBJECT TERMS Caregiver, Care Provider, Secondary Traumatic Stress, Combat Trauma, Shared Trauma, Posttraumatic Stress Disorder, Burnout 16

Treating Selective Mutism Using Modular CBT for Child Anxiety: A Case Study

ERIC Educational Resources Information Center

Reuther, Erin T.; Davis, Thompson E., III; Moree, Brittany N.; Matson, Johnny L.

2011-01-01

Selective mutism is a rare, debilitating condition usually seen in children. Unfortunately, there is little research examining effective treatments for this disorder, and designing an evidence-based treatment plan can be difficult. This case study presents the evidence-based treatment of an 8-year-old Caucasian boy with selective mutism using an…

Service-Learning with the Mentally Ill: Softening the Stigma

ERIC Educational Resources Information Center

Barney, Steve T.; Corser, Grant C.; White, Lynn H.

2010-01-01

Stigmas toward those who have mental illnesses are wide-spread and detrimental to the health and well-being of those suffering from these debilitating conditions, and to society as a whole. Stigma-reducing programs are plentiful but many are only marginally effective. In this paper we describe and evaluate a course in Psychopathology that included…

Monoclonal antibodies passively protect BALB/c mice against Burkholderia mallei aerosol challenge.

PubMed

Treviño, Sylvia R; Permenter, Amy R; England, Marilyn J; Parthasarathy, Narayanan; Gibbs, Paul H; Waag, David M; Chanh, Tran C

2006-03-01

Glanders is a debilitating disease with no vaccine available. Murine monoclonal antibodies were produced against Burkholderia mallei, the etiologic agent of glanders, and were shown to be effective in passively protecting mice against a lethal aerosol challenge. The antibodies appeared to target lipopolysaccharide. Humoral antibodies may be important for immune protection against B. mallei infection.

The Awful Truth: A Microhistory of Teacher Stress at Westwood High

ERIC Educational Resources Information Center

Munt, Valerie

2004-01-01

This paper is drawn from a recent microhistory of teacher stress, a genealogical inquiry that reveals the debilitating effects of a 'game of truth' called 'economic rationalism' on South Australian teachers during the last two decades of the twentieth century. It explores the everyday stresses of teaching through extracts from the teachers' oral…

Experimental Therapeutics Against the Toxic and Lethal Effects Resulting from Acute Exposure to Nerve Agents Without Carbamate Pretreatment in Guinea Pigs

DTIC Science & Technology

2010-09-01

or VX. Guinea pigs chronically instrumented for concurrent recordings of EEG, cardiorespiratory activities , diaphragm and skeletal muscle EMG were... activities , or any debilitating effects. The animals were asymptomatic within 30 min following therapy and survived the agent challenge 24 hr later. In...For a thorough efficacy evaluation, the animals were chronically instrumented to permit concurrent recordings of central nervous system activity

Once-daily USL255 as adjunctive treatment of partial-onset seizures: Randomized phase III study

PubMed Central

Chung, Steve S; Fakhoury, Toufic A; Hogan, R Edward; Nagaraddi, Venkatesh N; Blatt, Ilan; Lawson, Balduin; Arnold, Stephan; Anders, Bob; Clark, Annie M; Laine, Dawn; Meadows, R Shawn; Halvorsen, Mark B

2014-01-01

Objective To evaluate the efficacy and safety of USL255, Qudexy™ XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs. Methods In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated. Results Across the entire 11-week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life. Significance The PREVAIL phase III clinical study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects. PMID:24902983

Novel transparent conductor with enhanced conductivity: hybrid of silver nanowires and dual-doped graphene

NASA Astrophysics Data System (ADS)

Sohn, Hiesang; Woo, Yun Sung; Shin, Weonho; Yun, Dong-Jin; Lee, Taek; Kim, Felix Sunjoo; Hwang, Jinyoung

2017-10-01

We present hybrid transparent conducting films based on silver nanowires (Ag NWs) and doped graphene through novel dual co-doping method by applying various dopants (HNO3 or Au for p-doping and N2H4 for n-doping) on top and bottom sides of graphene. We systematically investigated the effect of dual-doping on their surface as well as electrical and optical properties of graphene and Ag NW/graphene hybrid films through the combination study with various dopant types (p/p, p/n, n/p, and n/n). We found that the p/p-type dual-doped (p-type dopant: HNO3) graphene and its hybrid formation with Ag NWs appeared to be the most effective in enhancing the electrical properties of conductor (doped graphene with ΔR/R0 = 84% and Ag NW/doped graphene hybrid with ΔR/R0 = 62%), demonstrating doped monolayer graphene with high optical transmittance (TT = 97.4%), and sheet resistance (Rs = 188 Ω/sq.). We also note that dual-doping improved such electrical properties without any significant debilitation of optical transparency of conductors (doped graphene with ΔTT = 0.1% and Ag NW/doped graphene hybrid with ΔTT = 0.4%). In addition, the enhanced conductivity of p-type dual-doped graphene allows a hybrid system to form co-percolating network in which Ag NWs can form a secondary conductive path at grain boundaries of polycrystalline graphene.

Design and preliminary testing of a handheld antagonistic SMA actuator for cancellation of human tremor

NASA Astrophysics Data System (ADS)

Pathak, Anupam; Brei, Diann; Luntz, Jonathan

2009-03-01

Essential Tremor is a debilitating disorder that in the US alone is estimated to affect up to ten million people. Unfortunately current treatments (i.e. drug therapy and surgical procedures), are limited in effectiveness and often pose a risk of adverse side-effects. In response to this problem, this paper describes an active cancellation device based on a hand-held Shape Memory Alloy (SMA) actuated stabilization platform. The assistive device is designed to hold and stabilize various objects (e.g. eating utensils, tools, pointing implements, etc.) by sensing the user's tremor and moving the object in an opposite direction using SMA actuators configured in biologically inspired antagonistic pairs. To aid in the design, performance prediction and control of the device, a device model is described that accounts for the device kinematics, SMA thermo-mechanics, and the heat transfer resulting from electrical heating and convective cooling. The system of differential equations in this device model coupled with the controller gain can be utilized to design the operation given a frequency range and power requirement. To demonstrate this, a prototype was built and experimentally tested under external disturbances in the range of 1-5 Hz, resulting in amplitude reduction of up to 80%. The extent of cancellation measured for both single-frequencies and actual human tremor disturbances demonstrate the promise of this approach as a broadly used assistive device for the multitudes afflicted by tremor.

Athletic pubalgia and "sports hernia": optimal MR imaging technique and findings.

PubMed

Omar, Imran M; Zoga, Adam C; Kavanagh, Eoin C; Koulouris, George; Bergin, Diane; Gopez, Angela G; Morrison, William B; Meyers, William C

2008-01-01

Groin injuries are common in athletes who participate in sports that require twisting at the waist, sudden and sharp changes in direction, and side-to-side ambulation. Such injuries frequently lead to debilitating pain and lost playing time, and they may be difficult to diagnose. Diagnostic confusion often arises from the complex anatomy and biomechanics of the pubic symphysis region, the large number of potential sources of groin pain, and the similarity of symptoms in athletes with different types or sites of injury. Many athletes with a diagnosis of "sports hernia" or "athletic pubalgia" have a spectrum of related pathologic conditions resulting from musculotendinous injuries and subsequent instability of the pubic symphysis without any finding of inguinal hernia at physical examination. The actual causal mechanisms of athletic pubalgia are poorly understood, and imaging studies have been deemed inadequate or unhelpful for clarification. However, a large-field-of-view magnetic resonance (MR) imaging survey of the pelvis, combined with high-resolution MR imaging of the pubic symphysis, is an excellent means of assessing various causes of athletic pubalgia, providing information about the location of injury, and delineating the severity of disease. Familiarity with the pubic anatomy and with MR imaging findings in athletic pubalgia and in other confounding causes of groin pain allows accurate imaging-based diagnoses and helps in planning treatment that targets specific pathologic conditions. (c) RSNA, 2008.

The effects of BMY-14802 against L-DOPA- and dopamine agonist-induced dyskinesia in the hemiparkinsonian rat

PubMed Central

Bhide, Nirmal; Lindenbach, David; Surrena, Margaret A.; Goldenberg, Adam A.; Bishop, Christopher; Berger, S. Paul; Paquette, Melanie A.

2013-01-01

Rationale L-DOPA continues to be the primary treatment for patients with Parkinson’s disease; however, the benefits of long-term treatment are often accompanied by debilitating side effects known as dyskinesias. In recent years, several 5-HT1A receptor agonists have been found to reduce dyskinesia in clinical and experimental models of PD. The purported sigma-1 antagonist, BMY-14802 has been previously demonstrated to reduce L-DOPA induced dyskinesia in a 5-HT1A receptor dependent manner. Objective In the present study, we extend these findings by examining the anti-dyskinetic potential of BMY-14802 against L-DOPA, the D1 receptor agonist SKF81297 and the D2 receptor agonist, Quinpirole, in the hemi-parkinsonian rat model. In addition, the receptor specificity of BMY-14802’s effects was evaluated using WAY-100635, a 5-HT1A receptor antagonist. Results Results confirmed the dose-dependent (20>10>5 mg/kg) anti-dyskinetic effects of BMY-14802 against L-DOPA with preservation of antiparkinsonian efficacy at 10 mg/kg. BMY-14802 at 10 and 20 mg/kg also reduced dyskinesia induced by both D1 and D2 receptor agonists. Additionally, BMY-14802’s anti-dyskinetic effects against L-DOPA, but not SKF81297 or Quinpirole, were reversed by WAY-100635 (0.5 mg/kg). Conclusion Collectively, these findings demonstrate that BMY-14802 provides anti-dyskinetic relief against L-DOPA and direct DA agonist in a preclinical model of PD, acting via multiple receptor systems and supports the utility of such compounds for the improved treatment of PD. PMID:23389756

Simulating the Spread of an Outbreak of Foot and Mouth Disease in California

DTIC Science & Technology

2012-06-01

the disease, but it debilitates them; leading to severely decreased meat and milk production. The economic impact on a country with an FMD...of an infected animal. Most adult animals recover from the disease, but it debilitates them, which leads to severely decreased meat and milk ...the model, we include one randomly selected cattle premise from Central California without a time until detection in this file. This premise is a Cow

Natriuretic Peptides, 6-Min Walk Test, and Quality-of-Life Questionnaires as Clinically Meaningful Endpoints in HF Trials.

PubMed

Ferreira, João Pedro; Duarte, Kevin; Graves, Todd L; Zile, Michael R; Abraham, William T; Weaver, Fred A; Lindenfeld, JoAnn; Zannad, Faiez

2016-12-20

The Expedited Access for Premarket Approval and De Novo Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions document was issued as a guidance for industry and for the Food and Drug Administration. The Expedited Access Pathway was designed as a new program for medical devices that demonstrated the potential to address unmet medical needs for life threatening or irreversibly debilitating conditions. The Food and Drug Administration would consider assessments of a device's effect on intermediate endpoints that, when improving in a congruent fashion, are reasonably likely to predict clinical benefit. The purpose of this review is to provide evidence to support the use of 3 such intermediate endpoints: natriuretic peptides, such as N-terminal pro-B-type natriuretic peptide/B-type natriuretic peptide, the 6-min walk test distance, and health-related quality of life in heart failure. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Tinnitus and hyperacusis involve hyperactivity and enhanced connectivity in auditory-limbic-arousal-cerebellar network

PubMed Central

Chen, Yu-Chen; Li, Xiaowei; Liu, Lijie; Wang, Jian; Lu, Chun-Qiang; Yang, Ming; Jiao, Yun; Zang, Feng-Chao; Radziwon, Kelly; Chen, Guang-Di; Sun, Wei; Krishnan Muthaiah, Vijaya Prakash; Salvi, Richard; Teng, Gao-Jun

2015-01-01

Hearing loss often triggers an inescapable buzz (tinnitus) and causes everyday sounds to become intolerably loud (hyperacusis), but exactly where and how this occurs in the brain is unknown. To identify the neural substrate for these debilitating disorders, we induced both tinnitus and hyperacusis with an ototoxic drug (salicylate) and used behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) techniques to identify the tinnitus–hyperacusis network. Salicylate depressed the neural output of the cochlea, but vigorously amplified sound-evoked neural responses in the amygdala, medial geniculate, and auditory cortex. Resting-state fMRI revealed hyperactivity in an auditory network composed of inferior colliculus, medial geniculate, and auditory cortex with side branches to cerebellum, amygdala, and reticular formation. Functional connectivity revealed enhanced coupling within the auditory network and segments of the auditory network and cerebellum, reticular formation, amygdala, and hippocampus. A testable model accounting for distress, arousal, and gating of tinnitus and hyperacusis is proposed. DOI: http://dx.doi.org/10.7554/eLife.06576.001 PMID:25962854

Isolated displaced non-union of a triquetral body fracture: a case report

PubMed Central

2012-01-01

Introduction Fractures of the body of the triquetral bone are the second most common carpal fractures, and these fractures can be missed on plain X-ray. Although non-union of triquetral body fractures is very rare, such cases are associated with considerable morbidity and reduction in functional activity. Case presentation We report the case of a 29-year-old Caucasian British man who sustained an isolated displaced triquetral body fracture that resulted in non-union, who was treated surgically. We describe an original operative management for this debilitating injury. An open reduction and internal fixation using double headed compression screws was performed, without bone grafting, and with early immobilization of the wrist. Conclusions We propose this novel approach and advocate early clinical suspicion of triquetral body fractures in patients with a history of fall on an outstretched hand and ulnar sided wrist pain. We recommend evaluation using computed tomography or magnetic resonance imaging scanning. PMID:22325450

Safe and targeted anticancer therapy for ovarian cancer using a novel class of curcumin analogs

PubMed Central

2013-01-01

A diagnosis of advanced ovarian cancer is the beginning of a long and arduous journey for a patient. Worldwide, approximately half of the individuals undergoing therapy for advanced cancer will succumb to the disease, or consequences of treatment. Well-known and widely-used chemotherapeutic agents such as cisplatin, paclitaxel, 5-fluorouracil, and doxorubicin are toxic to both cancer and non-cancerous cells, and have debilitating side effects Therefore, development of new targeted anticancer therapies that can selectively kill cancer cells while sparing the surrounding healthy tissues is essential to develop more effective therapies. We have developed a new class of synthetic curcumin analogs, diarylidenyl-piperidones (DAPs), which have higher anticancer activity and enhanced bio-absorption than curcumin. The DAP backbone structure exhibits cytotoxic (anticancer) activity, whereas the N-hydroxypyrroline (-NOH) moiety found on some variants functions as a cellular- or tissue-specific modulator (antioxidant) of cytotoxicity. The anticancer activity of the DAPs has been evaluated using a number of ovarian cancer cell lines, and the safety has been evaluated in a number of non-cancerous cell lines. Both variations of the DAP compounds showed similar levels of cell death in ovarian cancer cells, however the compounds with the -NOH modification were less toxic to non-cancerous cells. The selective cytotoxicity of the DAP–NOH compounds suggests that they will be useful as safe and effective anticancer agents. This article reviews some of the key findings of our work with the DAP compounds, and compares this to some of the targeted therapies currently used in ovarian cancer therapy. PMID:23663277

Potential for Intrathecal Baclofen in Treatment of Essential Tremor.

PubMed

Hamad, Mousa; Holland, Ryan; Kamal, Naveed; Luceri, Robert; Mammis, Antonios

2017-09-01

Essential tremor (ET) is the most common movement disorder of adults, affecting an estimated 7 million Americans. Symptoms of ET range from slightly noticeable to debilitating, with 1 cohort study finding 15% of patients were forced into early retirement. Additionally, depression has also been correlated with the severity of disability of ET. Treatment options include propranolol and primidone. Current treatment options are not very effective, with more than half (56.3%) of patients discontinuing medications because of no changes in symptoms. Unfortunately, there is a relative void and controversy in the literature explaining ET pathophysiology; however, the gamma-aminobutyric acid (GABA) hypothesis is the strongest. We conducted a PubMed search on 30 September 2015 with no time constraints using the search terms "essential tremor" and "baclofen," which resulted in a total of 5 articles. Neurohistopathologic studies have demonstrated decreased GABA-A and GABA-B receptors in the cerebellar cortex of ET patients. GABA, the major inhibitory neurotransmitter in the central nervous system, is proposed to have an inhibitory effect on pacemaker output activity of the cerebello-thalamo-cortical pathway, with lower receptors resulting in decreased inhibition of baseline tremors. Tariq et al showed delayed onset and intensity of tremor with oral administration of R-baclofen in a mouse model of ET. With a better side-effect profile and success in a physiologically related condition, we propose more clinical trials and research be carried out on intrathecal baclofen as a potential treatment option, especially drug refractory ET, so as to increase the quality of life of this patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibiting DNA-PK{sub CS} radiosensitizes human osteosarcoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mamo, Tewodros; Mladek, Ann C.; Shogren, Kris L.

Osteosarcoma survival rate has not improved over the past three decades, and the debilitating side effects of the surgical treatment suggest the need for alternative local control approaches. Radiotherapy is largely ineffective in osteosarcoma, indicating a potential role for radiosensitizers. Blocking DNA repair, particularly by inhibiting the catalytic subunit of DNA-dependent protein kinase (DNA-PK{sub CS}), is an attractive option for the radiosensitization of osteosarcoma. In this study, the expression of DNA-PK{sub CS} in osteosarcoma tissue specimens and cell lines was examined. Moreover, the small molecule DNA-PK{sub CS} inhibitor, KU60648, was investigated as a radiosensitizing strategy for osteosarcoma cells in vitro. DNA-PK{submore » CS} was consistently expressed in the osteosarcoma tissue specimens and cell lines studied. Additionally, KU60648 effectively sensitized two of those osteosarcoma cell lines (143B cells by 1.5-fold and U2OS cells by 2.5-fold). KU60648 co-treatment also altered cell cycle distribution and enhanced DNA damage. Cell accumulation at the G2/M transition point increased by 55% and 45%, while the percentage of cells with >20 γH2AX foci were enhanced by 59% and 107% for 143B and U2OS cells, respectively. These results indicate that the DNA-PK{sub CS} inhibitor, KU60648, is a promising radiosensitizing agent for osteosarcoma. - Highlights: • DNA-PKcs is consistently expressed in human osteosarcoma tissue and cell lines. • The DNA-PKcs inhibitor, KU60648, effectively radiosensitizes osteosarcoma cells. • Combining KU60648 with radiation increases G2/M accumulation and DNA damage.« less

Cognitive changes associated with cancer and cancer treatment: state of the science.

PubMed

Von Ah, Diane

2015-02-01

Cognitive impairment is a distressing, disruptive, and potentially debilitating symptom that can occur as a direct result of cancer or its treatment. National organizations have identified cognitive impairment as a challenge many survivors face and call for research to address this problem. Despite the priority, research is still relatively limited and questions remain unanswered about prevalence and impact on survivors, as well as coping strategies and effective treatment options available to address this potentially debilitating problem. The purpose of this article is to (a) analyze the prevalence and types of cognitive impairment that commonly affect survivors; (b) delineate the impact that cognitive impairment after cancer and cancer treatment has on self-esteem, social relationships, work ability, and overall quality of life among survivors; and (c) synthesize and appraise commonly used coping strategies used by survivors to address cognitive impairment and evidence-based interventions that may be incorporated into clinical practice. A comprehensive review and synthesis of the literature was conducted. Evidence-based interventions to address cognitive changes after cancer and cancer treatment are limited. However, emerging research has demonstrated that nonpharmacologic treatments, such as cognitive training, are likely to be effective.

Controlling scabies in institutional settings: a review of medications, treatment models, and implementation.

PubMed

Scheinfeld, Noah

2004-01-01

Scabies is a global problem and a significant source of morbidity in nursing home residents and workers because of its highly contagious nature. It is also a problem in hospitals that care for the elderly, the debilitated, and the immunocompromised. New outbreaks continue to occur, despite controlling the recurrent epidemics. Scabies manifests as papules, pustules, burrows, nodules, and occasionally urticarial papules and plaques. Most of the patients with scabies experience severe pruritus. A subset of patients have crusted or Norwegian scabies. These patients, who are usually debilitated or immunocompromised, do not experience the urge to scratch, and therefore do not scratch their own skin. Diagnosis of scabies is based on patient history, physical examination, and demonstration of mites, eggs, or scybala (black or brown football-shaped masses of feces of scabies) on microscopic examination. Scabies can be treated with topical or oral therapies. Topical treatments include 5% permethrin cream, 1% lindane (gamma benzene hexachloride) lotion, 6% precipitated sulfur in petrolatum, crotamiton, malathion, allethrin spray, and benzyl benzoate. Ivermectin, the only oral treatment, is not approved for scabies in the US. Most authorities advocate using a scabicide several times, specifically once a week over a period of 2-3 weeks. In an outbreak of scabies in a nursing home, residents, staff, and frequent visitors should all be treated even if they are not symptomatic. Ivermectin is useful in treating patients with Norwegian or crusted scabies, or who are debilitated. Ivermectin has no serious reported adverse effects. Model treatment plans to stop scabies epidemics have been developed. These plans coordinate treatment of all persons exposed (including ivermectin for debilitated patients), isolation of infected patients, disinfection of objects that patients have come into contact with, and education and reassurance of the medical staff. Failure to coordinate notification, education, treatment, and disinfection leads to failure to control scabies epidemics. Control of epidemics of institutional scabies requires attention to treatment effects and logistics. Treatment is low risk, but cumbersome because many individuals need be treated. It is advisable to restrict, where possible, the number of staff members that deal with scabies patients to limit the spread of the scabies. Prolonged surveillance is required for the eradication of institutional scabies. While the foregoing plans require coordination of all involved personnel and sustained efforts, they are necessary to halt the spread of scabies to patients and staff, to enhance their morale, and to prevent deterioration of labor and public relations.

Predictors of host specificity among behavior-manipulating parasites.

PubMed

Fredensborg, B L

2014-07-01

A trade-off between resource-specialization and the breadth of the ecological niche is one of the most fundamental biological characteristics. A true generalist (Jack-of-all-trades) displays a broad ecological niche with little resource specialization while the opposite is true for a resource-specialist that has a restricted ecological niche that it masters. Parasites that manipulate hosts' behavior are often thought to represent resource-specialists based on a few spectacular examples of manipulation of the host's behavior. However, the determinants of which, and how many, hosts a manipulating parasite can exploit (i.e., niche breadth) are basically unknown. Here, I present an analysis based on published records of the use of hosts by 67 species from 38 genera of helminths inducing parasite increased trophic transmission, a widespread strategy of parasites that has been reported from many taxa of parasites and hosts. Using individual and multivariate analyses, I examined the effect of the host's and parasite's taxonomy, location of the parasite in the host, type of behavioral change, and the effect of debilitation on host-specificity, measured as the mean taxonomic relatedness of hosts that a parasite can manipulate. Host-specificity varied substantially across taxa suggesting great variation in the level of resource-specialization among manipulating parasites. Location of the parasite, level of debilitation, and type of host were all significant predictors of host-specificity. More specifically, hosts' behavioral modification that involves interaction with the central nervous system presumably restricts parasites to more closely related hosts than does manipulation of the host's behavior via debilitation of the host's physiology. The results of the analysis suggest that phylogenetic relatedness of hosts is a useful measure of host-specificity in comparative studies of the complexity of interactions taking place between manipulating parasites and their hosts. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.

PubMed

Kyte, S Lauren; Toma, Wisam; Bagdas, Deniz; Meade, Julie A; Schurman, Lesley D; Lichtman, Aron H; Chen, Zhi-Jian; Del Fabbro, Egidio; Fang, Xianjun; Bigbee, John W; Damaj, M Imad; Gewirtz, David A

2018-01-01

Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments. Our studies were designed to investigate whether nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor cell proliferation or interfere with the antitumor properties of paclitaxel. Male C57BL/6J mice received paclitaxel every other day for a total of four injections (8 mg/kg, i.p.). Acute (0.3-0.9 mg/kg, i.p.) and chronic (24 mg/kg per day, s.c.) administration of nicotine respectively reversed and prevented paclitaxel-induced mechanical allodynia. Blockade of the antinociceptive effect of nicotine with mecamylamine and methyllycaconitine suggests that the reversal of paclitaxel-induced mechanical allodynia is primarily mediated by the α 7 nicotinic acetylcholine receptor subtype. Chronic nicotine treatment also prevented paclitaxel-induced intraepidermal nerve fiber loss. Notably, nicotine neither promoted proliferation of A549 and H460 non-small cell lung cancer cells nor interfered with paclitaxel-induced antitumor effects, including apoptosis. Most importantly, chronic nicotine administration did not enhance Lewis lung carcinoma tumor growth in C57BL/6J mice. These data suggest that the nicotinic acetylcholine receptor-mediated pathways may be promising drug targets for the prevention and treatment of CIPN. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

The effect of sour tea (Hibiscus sabdariffa) on essential hypertension.

PubMed

Haji Faraji, M; Haji Tarkhani, A

1999-06-01

Considering the high prevalence of hypertension, its debilitating end organ damage, and the side effects of chemical drugs used for its treatment, we conducted this experimental study to evaluate the effect of sour tea (Hibiscus sabdariffa) on essential hypertension. For this purpose, 31 and 23 patients with moderate essential hypertension were randomly assigned to an experimental and control group, respectively. Patients with secondary hypertension or those consuming more than two drugs were excluded from the study. Systolic and diastolic blood pressures were measured before and 15 days after the intervention. In the experimental group, 45% of the patients were male and 55% were female, and the mean age was 52.6 +/- 7.9 years. In the control group, 30% of the patients were male, 70% were female, and the mean age of the patients was 51.5 +/- 10.1 years. Statistical findings showed an 11.2% lowering of the systolic blood pressure and a 10.7% decrease of diastolic pressure in the experimental group 12 days after beginning the treatment, as compared with the first day. The difference between the systolic blood pressures of the two groups was significant, as was the difference of the diastolic pressures of the two groups. Three days after stopping the treatment, systolic blood pressure was elevated by 7.9%, and diastolic pressure was elevated by 5.6% in the experimental and control groups. This difference between the two groups was also significant. This study proves the public belief and the results of in vitro studies concerning the effects of sour tea on lowering high blood pressure. More extensive studies on this subject are needed.

Facilitating and debilitating trait anxiety, situational anxiety, and coping with an anticipated stressor: a process analysis.

PubMed

Raffety, B D; Smith, R E; Ptacek, J T

1997-04-01

Participants completed anxiety and coping diaries during 10 periods that began 7 days before an academic stressor and continued through the evening after the stressor. Profile analysis was used to examine the anxiety and coping processes in relation to 2 trait anxiety grouping variables: debilitating and facilitating test anxiety (D-TA and F-TA). Anxiety and coping changed over time, and high and low levels of D-TA and F-TA were associated with different daily patterns of anxiety and coping. Participants with a debilitative, as opposed to facilitative, trait anxiety style had lower examination scores, higher anxiety, and less problem-solving coping. Covarying F-TA, high D-TA was associated with a pattern of higher levels of tension, worry, distraction, and avoidant coping, as well as lower levels of proactive coping. Covarying D-TA, high F-TA was associated with higher levels of tension (but not worry or distraction), support seeking, proactive and problem-solving coping.

3D ultrasound Nakagami imaging for radiation-induced vaginal fibrosis

NASA Astrophysics Data System (ADS)

Yang, Xiaofeng; Rossi, Peter; Shelton, Joseph; Bruner, Debrorah; Tridandapani, Srini; Liu, Tian

2014-03-01

Radiation-induced vaginal fibrosis is a debilitating side-effect affecting up to 80% of women receiving radiotherapy for their gynecological (GYN) malignancies. Despite the significant incidence and severity, little research has been conducted to identify the pathophysiologic changes of vaginal toxicity. In a previous study, we have demonstrated that ultrasound Nakagami shape and PDF parameters can be used to quantify radiation-induced vaginal toxicity. These Nakagami parameters are derived from the statistics of ultrasound backscattered signals to capture the physical properties (e.g., arrangement and distribution) of the biological tissues. In this paper, we propose to expand this Nakagami imaging concept from 2D to 3D to fully characterize radiation-induced changes to the vaginal wall within the radiation treatment field. A pilot study with 5 post-radiotherapy GYN patients was conducted using a clinical ultrasound scanner (6 MHz) with a mechanical stepper. A serial of 2D ultrasound images, with radio-frequency (RF) signals, were acquired at 1 mm step size. The 2D Nakagami shape and PDF parameters were calculated from the RF signal envelope with a sliding window, and then 3D Nakagami parameter images were generated from the parallel 2D images. This imaging method may be useful as we try to monitor radiation-induced vaginal injury, and address vaginal toxicities and sexual dysfunction in women after radiotherapy for GYN malignancies.

[The mind and epilepsy: opinions and viewpoints over the course of time].

PubMed

Vaney, C

1989-07-18

Among the very few diseases that can be traced back to ancient times none has stimulated human phantasy as much as epilepsy, and the many names given to epilepsy reflects the different trends of thinking on the topic over the past two and a half thousand years. The ancient Greek believed epilepsy to be a sacred disease with the body being invaded by a God. The view that demons and evil spirits rather than Gods were responsible for the disease prevailed throughout the middle ages, influenced by Christian thinking. This led people with epilepsy to be treated, as the mentally ill, with contempt and pity. Up to the latter half of the 19th century epilepsy remained an integral part of psychiatry. The concept of the epileptic personality, stating that the behaviour and consequently the seizures themselves came from a constitutional hereditary psychopathic make-up, was deeply entrenched. The process of distinguishing epilepsy from insanity began with the development of neurology as a new and independent discipline, helped by the discovery of electroencephalography EEG and potent antiepileptic drugs. It became more widely accepted that most epileptic patients have normal mental states. It was argued that the psychiatric consequences of having epilepsy depended on the existence of pathological brain lesions, side-effects of inadequate drugs and the psychological stress of living with a chronic and debilitating disease.

The DNA helicase–primase complex as a target for herpes viral infection

PubMed Central

Weller, Sandra K; Kuchta, Robert D

2014-01-01

Introduction The Herpesviridae are responsible for debilitating acute and chronic infections, and some members of this family are associated with human cancers. Conventional anti-herpesviral therapy targets the viral DNA polymerase and has been extremely successful; however, the emergence of drug-resistant virus strains, especially in neonates and immunocompromised patients, underscores the need for continued development of anti-herpes drugs. In this article, we explore an alternative target for antiviral therapy, the HSV helicase/primase complex. Areas covered This review addresses the current state of knowledge of HSV DNA replication and the important roles played by the herpesvirus helicase–primase complex. In the last 10 years several helicase/primase inhibitors (HPIs) have been described, and in this article, we discuss and contrast these new agents with established inhibitors. Expert opinion The outstanding safety profile of existing nucleoside analogues for a-herpesvirus infection make the development of new therapeutic agents a challenge. Currently used nucleoside analogues exhibit few side effects and have low occurrence of clinically relevant resistance. For HCMV, however, existing drugs have significant toxicity issues and the frequency of drug resistance is high, and no antiviral therapies are available for EBV and KSHV. The development of new anti-herpesvirus drugs is thus well worth pursuing especially for immunocompromised patients and those who develop drug-resistant infections. Although the HPIs are promising, limitations to their development into a successful drug strategy remain. PMID:23930666

Successful Use of Rasagiline in Combination with Two Antidepressants

PubMed Central

Madan, Rohit; Sharma, Ashish

2012-01-01

Parkinson’s disease is the second most common neurodegenerative disorder, affecting 1 to 2 percent of people older than 60 years. Recent reviews show that depression is a common and potentially debilitating aspect of Parkinson’s disease, affecting 40 to 50 percent of patients. Depression in Parkinson’s disease is demonstrably different from ordinary major depression in terms of gender ratio, age, symptom profile, comorbidity, and chronicity. Pharmacotherapy for depression in Parkinson’s disease entails special concerns related to side effects and drug-drug interactions. Rasagiline is a novel, potent, and irreversible monoamine oxidase type B (MAO-B) inhibitor that has recently been approved by the Food and Drug Administration for treatment of Parkinson’s disease. Current rasagiline labeling advises the avoidance of coadministration of rasagiline and antidepressants, which is a challenge in itself for patients with co-morbid depression. We present a case of a 58-year-old woman who failed most of the pharmacologic treatments for Parkinson’s disease, including deep brain stimulation, and was recently prescribed rasagiline with good response. She also met the Diagnostic and Statistical Manual, Fourth Edition, Text Revision criteria of major depressive disorder, which was treated with venlafaxine and bupropion. To our knowledge, this is first clinical case report of successful use of a combination of antidepressants and rasagiline in a patient with Parkinson’s disease. PMID:23346517

Glucocorticoids in the management of systemic juvenile idiopathic arthritis.

PubMed

Vannucci, Gaia; Cantarini, Luca; Giani, Teresa; Marrani, Edoardo; Moretti, Davide; Pagnini, Ilaria; Simonini, Gabriele; Cimaz, Rolando

2013-10-01

Glucocorticoids have been the mainstay of treatment for many years in systemic-onset juvenile idiopathic arthritis (sJIA), causing important side effects and some difficulties in the management of this disease. Until the introduction of biologic agents, oral glucocorticoids were used to control fever and other systemic features for several months or even years if systemic manifestations persisted. Nowadays, clinicians have valid alternatives that have revolutionized the natural history of sJIA. Biologic agents, such as the interleukin-1 inhibitors anakinra and the more recent canakinumab, or the interleukin-6 inhibitor tocilizumab, have improved the prognosis of this debilitating disease. Glucocorticoids still have to be considered at the onset of disease when a non-steroidal anti-inflammatory drug therapy fails or when there are life-threatening complications such as severe anemia or pericarditis, or macrophage activation syndrome. Local (intra-articular) triamcinolone hexacetonide is the treatment of choice for arthritis limited to one joint or a few joints in patients without systemic activity. To date, there is still great heterogeneity in the management of sJIA patients, but in recent years there have been attempts to design algorithms and treatment protocols for glucocorticoids, disease-modifying anti-rheumatic drugs, and biologic agents. This review provides an overview of the current knowledge of glucocorticoid therapy in sJIA, comments on recently published recommendations, and gives practical support to the clinician for management of this disease.

Role of Complement in a Rat Model of Paclitaxel-Induced Peripheral Neuropathy.

PubMed

Xu, Jijun; Zhang, Lingjun; Xie, Mian; Li, Yan; Huang, Ping; Saunders, Thomas L; Fox, David A; Rosenquist, Richard; Lin, Feng

2018-06-15

Chemotherapy-induced peripheral neuropathy (CIPN) is a painful and debilitating side effect of cancer chemotherapy with an unclear pathogenesis. Consequently, the available therapies for this neuropathic pain syndrome are inadequate, leading to a significantly reduced quality of life in many patients. Complement, a key component of the innate immune system, has been associated with neuroinflammation, a potentially important trigger of some types of neuropathic pain. However, the role of complement in CIPN remains unclear. To address this issue, we developed a C3 knockout (KO) rat model and induced CIPN in these KO rats and wild-type littermates via the i.p. administration of paclitaxel, a chemotherapeutic agent associated with CIPN. We then compared the severity of mechanical allodynia, complement activation, and intradermal nerve fiber loss between the groups. We found that 1) i.p. paclitaxel administration activated complement in wild-type rats, 2) paclitaxel-induced mechanical allodynia was significantly reduced in C3 KO rats, and 3) the paclitaxel-induced loss of intradermal nerve fibers was markedly attenuated in C3 KO rats. In in vitro studies, we found that paclitaxel-treated rat neuronal cells activated complement, leading to cellular injury. Our findings demonstrate a previously unknown but pivotal role of complement in CIPN and suggest that complement may be a new target for the development of novel therapeutics to manage this painful disease. Copyright © 2018 by The American Association of Immunologists, Inc.

Optimal control of directional deep brain stimulation in the parkinsonian neuronal network

NASA Astrophysics Data System (ADS)

Fan, Denggui; Wang, Zhihui; Wang, Qingyun

2016-07-01

The effect of conventional deep brain stimulation (DBS) on debilitating symptoms of Parkinson's disease can be limited because it can only yield the spherical field. And, some side effects are clearly induced with influencing their adjacent ganglia. Recent experimental evidence for patients with Parkinson's disease has shown that a novel DBS electrode with 32 independent stimulation source contacts can effectively optimize the clinical therapy by enlarging the therapeutic windows, when it is applied on the subthalamic nucleus (STN). This is due to the selective activation in clusters of various stimulation contacts which can be steered directionally and accurately on the targeted regions of interest. In addition, because of the serious damage to the neural tissues, the charge-unbalanced stimulation is not typically indicated and the real DBS utilizes charge-balanced bi-phasic (CBBP) pulses. Inspired by this, we computationally investigate the optimal control of directional CBBP-DBS from the proposed parkinsonian neuronal network of basal ganglia-thalamocortical circuit. By appropriately tuning stimulation for different neuronal populations, it can be found that directional steering CBBP-DBS paradigms are superior to the spherical case in improving parkinsonian dynamical properties including the synchronization of neuronal populations and the reliability of thalamus relaying the information from cortex, which is in a good agreement with the physiological experiments. Furthermore, it can be found that directional steering stimulations can increase the optimal stimulation intensity of desynchronization by more than 1 mA compared to the spherical case. This is consistent with the experimental result with showing that there exists at least one steering direction that can allow increasing the threshold of side effects by 1 mA. In addition, we also simulate the local field potential (LFP) and dominant frequency (DF) of the STN neuronal population induced by the activation of 32 different contacts with optimal stimulation intensity and immediately after the stimulation, respectively. These can reveal regional differences in pathological activity within STN nucleus. It is shown that in line with the experimental results directional steering stimulation can induce the low-amplitude LFP which implies the occurrence of desynchronizing regime, as well as the distribution of DF can locate at the 13-40 Hz of beta frequency range. Hopefully, the obtained results can provide theoretical evidences in exploring pathophysiologic activity of brain.

Carbofuran affects wildlife on Virginia corn fields

USGS Publications Warehouse

Stinson, E.R.; Hayes, L.E.; Bush, P.B.; White, D.H.

1994-01-01

Forty-four Virginia corn fields on 11 farms were searched for evidence of dead or debilitated wildlife following in-furrow application of granular carbofuran (Furadan 15G) during April and May 1991. Evidence of pesticide poisoned wildlife, including dead animals, debilitated animals, feather spots, and fur spots was found on 33 fields on 10 farms. Carcasses of 61 birds, 4 mammals, and 1 reptile were recovered. Anticholinesterase poisoning was confirmed or suspected as the cause of most wildlife deaths based on the circumstances surrounding kills, necropsies of Carcasses, residue analyses, and brain ChE assays.

Frequency and direction of competitive anger in contact sports.

PubMed

Robazza, B; Bertollo, M; Bortoli, L

2006-09-01

The purpose of the present study was to investigate whether athletes involved in physical contact sports may interpret their feelings of anger as facilitative of performance, and to examine differences in the interpretation of anger as a function of the type of sport (team vs individual) or the competitive skill level (high vs low). A modified version of the State-Trait Anger Expression Inventory was administered to 100 Italian adult male athletes practicing rugby or individual combat sports (judo, freestyle wrestling, or Greco-Roman wrestling). The questionnaire was intended to measure the frequency and the direction (i.e., the facilitative-debilitative interpretation) of competitive anger. Many athletes engaged in contact sports tended interpret their competitive anger as facilitative of performance rather than debilitative. The type of sport and the athlete's standard level can mediate the individual's interpretation of the effects of anger symptoms upon performance. Competitors can interpret their anger as helpful to energize behavior and channel physical and mental resources for skill execution. Practitioners should assist athletes in gaining control over anger rather than attempting to suppress it.

Coping styles for trait shame and anxiety intensity and direction in competitive athletes.

PubMed

Partridge, Julie A; Wiggins, Matthew S

2008-12-01

The purpose of the study was to assess if athletes who perceived their anxiety as debilitative to performance also scored higher on ratings of coping styles used to handle trait shame. The sample was comprised of 94 participants (males = 44, females = 50) ranging in age from 15 to 24 years (M = 18.8, SD = 2.3). Athletes in high school (n = 21) and college (n = 73) representing several sports were surveyed for this study. Competitive sport experience averaged 11 yr. (SD = 3.9) overall. The Competitive Trait Anxiety Inventory-2D was given to collect general anxiety perceptions related to the athlete's specific sport. The Compass of Shame Scale-Sport was administered to measure coping styles for trait shame responses connected with competitive sport experiences. The athletes were divided into Facilitative (n = 39) and Debilitative anxiety groups (n = 55) based on the overall direction of anxiety scores. Multivariate analysis of variance indicated no interaction, but did reveal significant main effects for sex and anxiety group. Univariate tests indicated significant differences for several of the shame and anxiety subscales based on sex and anxiety group.

Studies of third-order optical nonlinearities and optical limiting properties of azo dyes.

PubMed

Gayathri, C; Ramalingam, A

2008-03-01

In order to protect optical sensors and human eyes from debilitating laser effects, the intensity of the incoming laser light has to be opportunely reduced. Here, we report our results on the third-order optical nonlinearity and optical limiting properties of three azo dyes exposed to a 532nm continuous wave laser. We have observed low power optical limiting based on nonlinear refraction in our samples.

Quantification of larval resistance to Cypermethrin in tobacco budworm (Lepidoptera: Noctuidae) and the effects of larval weight

Treesearch

Michael J. Firko; Janes Leslie Hayes

1990-01-01

We examined relationships between larval weight and degree of resistance to cypermethrin in tobacco budworm, Heliothis virescens (F.). Laboratory-reared larvae (9.0-175.4 mg) were treated with either 0.1 or 1.0 mg cypermethrin in acetone. Degree of debilitation of each larva was assessed at intervals from 0.5 h to 5 d after treatment cumulative...

High-frequency repetitive transcranial magnetic stimulation over the left DLPFC for major depression: Session-dependent efficacy: A meta-analysis.

PubMed

Teng, S; Guo, Z; Peng, H; Xing, G; Chen, H; He, B; McClure, M A; Mu, Q

2017-03-01

Depression is a major debilitating psychiatric disorder. Current antidepressant drugs are often associated with side effects or treatment resistance. The aim of this meta-analysis was to evaluate therapeutic effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) in major depression (MD). The medical data bases of PubMed, Medline, Embase and Cochrane Central Register were searched for randomized controlled trials (RCTs) reporting the therapeutic effects of high-frequency rTMS for depression, which were published in English between January 1990 and June 2016. The index terms were "depress*", "depression" and "transcranial magnetic stimulation". Depression outcome data of different sessions (5, 10, 15, and 20 sessions of rTMS treatment) were extracted and synthesized by calculating standardized mean difference (SMD) with 95% confidence intervals (CI) by using a random-effect model. Within each session group, the subgroup analyses based on the number of pulses (≤1000, 1200-1500, 1600-1800, and 2000-3000) were also conducted. Thirty RCTs with a total of 1754 subjects including 1136 in the rTMS group and 618 in the sham group were included in this meta-analysis. rTMS had a significant overall therapeutic effect on depression severity scores (SMD=-0.73, P<0.00001). The five, 10, 15, 20 sessions of rTMS treatments yielded the significant mean effect sizes of -0.43, -0.60, -1.13, and -2.74, respectively. In the four groups (5, 10, 15, 20 sessions), the maximal mean effect size was all obtained in the subgroup of 1200-1500 pulses per day (-0.97, -1.14, -1.91, -5.47; P<0.05). The increasing of HF-rTMS sessions is associated with the increased efficacy of HF-rTMS in reducing depressed patients' symptom severity. A total number of pulses of 1200-1500 per day appear to deliver the best antidepressant effects of HF-rTMS. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Etiology and treatment of cough in idiopathic pulmonary fibrosis.

PubMed

Vigeland, Christine L; Hughes, Andrew H; Horton, Maureen R

2017-02-01

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of dysregulated wound healing leading to unremitting scarring and loss of lung function. The predominant symptoms are dyspnea on exertion and a persistent dry cough. For patients with IPF, cough is more than just bothersome; it has a significant negative impact on quality of life and is a marker of disease severity and progression. The etiology of cough in IPF is unclear but may be due to architectural distortion of the lungs, increased sensitivity of the cough reflex, airway inflammation, or changes in mucus production and clearance. There also may be an overlap between IPF cough and cough due to other common etiologies such as asthma, gastroesophageal reflux disease, upper airway cough syndrome, and medications. There are no approved therapies to specifically treat IPF cough, and recently approved medications for IPF have not been evaluated in cough. Few clinical trials have focused on treatments for IPF cough. To date, there is only one randomized, placebo control therapeutic study for IPF cough with thalidomide, which significantly reduced IPF cough and improved quality of life. Two additional cohort studies report that interferon-α and prednisolone also decrease IPF cough. However, no medication is approved to treat IPF cough. Currently, the mainstay of therapy for IPF cough is standard cough suppressants, which have limited efficacy and often intolerable side effects. Future studies are needed to determine an effective therapy to alleviate this particularly debilitating symptom and improve overall quality of life for patients suffering with IPF. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dichlorophenyl piperazines, including a recently-approved atypical antipsychotic, are potent inhibitors of DHCR7, the last enzyme in cholesterol biosynthesis.

PubMed

Genaro-Mattos, Thiago C; Tallman, Keri A; Allen, Luke B; Anderson, Allison; Mirnics, Karoly; Korade, Zeljka; Porter, Ned A

2018-06-15

While antipsychotic medications provide important relief from debilitating psychotic symptoms, they also have significant adverse side effects, which might have relevant impact on human health. Several research studies, including ours, have shown that commonly used antipsychotics such as haloperidol and aripiprazole affect cholesterol biosynthesis at the conversion of 7-dehydrocholesterol (7-DHC) to cholesterol. This transformation is promoted by the enzyme DHCR7 and its inhibition causes increases in plasma and tissue levels of 7-DHC. The inhibition of this enzymatic step by mutations in the Dhcr7 gene leads to Smith-Lemli-Opitz syndrome, a devastating human condition that can be replicated in rats by small molecule inhibitors of DHCR7. The fact that two compounds, brexpiprazole and cariprazine, that were recently approved by the FDA have substructural elements in common with the DHCR7 inhibitor aripiprazole, prompted us to evaluate the effect of brexpiprazole and cariprazine on cholesterol biosynthesis. We report that cariprazine affects levels of 7-DHC and cholesterol in cell culture incubations at concentrations as low as 5 nM. Furthermore, a common metabolite of cariprazine and aripiprazole, 2,3-(dichlorophenyl) piperazine, inhibits DHCR7 activity at concentrations comparable to those of the potent teratogen AY9944. The cell culture experiments were corroborated in mice in studies showing that treatment with cariprazine elevated 7-DHC in brain and serum. The consequences of sterol inhibition by antipsychotics in the developing nervous system and the safety of their use during pregnancy remains to be established. Copyright © 2018 Elsevier Inc. All rights reserved.

Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis

PubMed Central

Arosh, Joe A.; Lee, JeHoon; Balasubbramanian, Dakshnapriya; Stanley, Jone A.; Long, Charles R.; Meagher, Mary W.; Osteen, Kevin G.; Bruner-Tran, Kaylon L.; Burghardt, Robert C.; Starzinski-Powitz, Anna; Banu, Sakhila K.

2015-01-01

Endometriosis is a debilitating, estrogen-dependent, progesterone-resistant, inflammatory gynecological disease of reproductive age women. Two major clinical symptoms of endometriosis are chronic intolerable pelvic pain and subfertility or infertility, which profoundly affect the quality of life in women. Current hormonal therapies to induce a hypoestrogenic state are unsuccessful because of undesirable side effects, reproductive health concerns, and failure to prevent recurrence of disease. There is a fundamental need to identify nonestrogen or nonsteroidal targets for the treatment of endometriosis. Peritoneal fluid concentrations of prostaglandin E2 (PGE2) are higher in women with endometriosis, and this increased PGE2 plays important role in survival and growth of endometriosis lesions. The objective of the present study was to determine the effects of pharmacological inhibition of PGE2 receptors, EP2 and EP4, on molecular and cellular aspects of the pathogenesis of endometriosis and associated clinical symptoms. Using human fluorescent endometriotic cell lines and chimeric mouse model as preclinical testing platform, our results, to our knowledge for the first time, indicate that selective inhibition of EP2/EP4: (i) decreases growth and survival of endometriosis lesions; (ii) decreases angiogenesis and innervation of endometriosis lesions; (iii) suppresses proinflammatory state of dorsal root ganglia neurons to decrease pelvic pain; (iv) decreases proinflammatory, estrogen-dominant, and progesterone-resistant molecular environment of the endometrium and endometriosis lesions; and (v) restores endometrial functional receptivity through multiple mechanisms. Our novel findings provide a molecular and preclinical basis to formulate long-term nonestrogen or nonsteroidal therapy for endometriosis. PMID:26199416

Acoustic characteristics of underwater tail slaps used by Norwegian and Icelandic killer whales (Orcinus orca) to debilitate herring (Clupea harengus).

PubMed

Simon, Malene; Wahlberg, Magnus; Ugarte, Fernando; Miller, Lee A

2005-06-01

Norwegian killer whales debilitate prey by slapping their tails into herring schools. These underwater tail slaps produce a thud-like sound. It is unclear whether this sound is caused by cavitation and/or physical contact between herring and whale tail. Also the forces causing debilitation of the fish are not understood. Here we present an acoustic analysis of underwater tail slaps using a multi-channel wide (150 kHz) band recording system. Underwater tail slaps produced by Norwegian killer whales generated sounds consisting of multiple pulses with source levels of 186+/-5.4 dB (pp) re.1 microPa at 1 m (+/-1 s.d., N = 4). The -3 dB and 97% energy bandwidths were 36.8+/-22.5 kHz and 130.5+/-17.5 kHz (+/-1 s.d., N = 13), respectively, with a centre frequency of 46.1+/-22.3 kHz. The similarities between the acoustic properties of underwater tail slaps recorded from killer whales in Norway, and thud-like sounds recorded from killer whales in Iceland suggest that Norwegian and Icelandic killer whales use similar hunting techniques. The acoustic characteristics of sounds produced by underwater tail slaps were similar to the ones from other cavitation sound sources described in the literature, both in term of temporal and frequency features as well as in source level. We suggest that multiple factors generated by the tail slaps like particle fluctuations, turbulence, pressure changes and physical impact cause debilitation of herring.

Positive and negative mood in men with advanced prostate cancer undergoing androgen deprivation therapy: considering the role of social support and stress.

PubMed

Benedict, Catherine; Dahn, Jason R; Antoni, Michael H; Traeger, Lara; Kava, Bruce; Bustillo, Natalie; Zhou, Eric S; Penedo, Frank J

2015-08-01

Advanced prostate cancer patients often undergo androgen deprivation therapy (ADT). Advanced disease and adverse ADT side effects are often debilitating and negatively impact mood. Social support has been shown to mitigate detrimental effects of stress on mood. This study sought to characterize positive and negative mood in this select patient population and determine whether social support moderated relations between stress and mood. Participants (N = 80) completed the Interpersonal Support Evaluation List, Perceived Stress Scale, and Derogatis Affect Balance Scale at a single time point. Hierarchical regression models evaluated relations among social support, stress, and mood controlling for relevant covariates. Standard moderation analyses were performed. Participants reported higher levels of negative and positive mood compared with published means of localized prostate cancer patients. Overall, mood was more positive than negative. Stress levels were comparable to cancer populations with recurrent disease. Moderated regression analyses showed that social support partially buffered the effects of stress on positive mood; men with high stress and low support reported the lowest levels of positive mood. The model with negative mood as the dependent measure did not support moderation; that is, the relationship between stress and negative mood did not differ by level of social support. Among individuals living with advanced prostate cancer, social support may be an important factor that sustains positive mood in the presence of stress. Future work should examine the extent to which social support prospectively impacts health-related quality of life by promoting positive mood. Limitations include cross-sectional design, which precludes causal inferences. Copyright © 2014 John Wiley & Sons, Ltd.

Randomized trial of a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) on symptoms of benign prostatic hyperplasia (BPH).

PubMed

Preuss, H G; Marcusen, C; Regan, J; Klimberg, I W; Welebir, T A; Jones, W A

2001-01-01

Because benign prostatic hyperplasia (BPH) is relatively common, it is important to discover safe and effective means to treat this often debilitating perturbation. Accordingly, we examined the effectiveness of a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) in treating symptoms of BPH. We undertook a randomized, placebo-controlled, double-blind study. Patients were enrolled from 3 urological practices in the USA. 144 subjects were randomized for study. 17 subjects eventually withdrew, leaving 70 patients in the test group and 57 in the placebo group to complete the study. Inclusion criteria consisted of a diagnosis of BPH, no evidence of cancer, and a maximal urinary flow rate between 5 and 15 ml/second. Patients received either placebo or the combined natural products for 3 months. Evaluations were performed via the American Urological Association (AUA) Symptom Index score, urinary flow rate, PSA measurement, and residual bladder volume. Nocturia showed a markedly significant decrease in severity in patients receiving the combined natural products compared to those taking placebo (p < 0.001). Daytime frequency was also lessened significantly (p < 0.04). When the average individual total AUA Symptom Index score in the test group was compared to that in the placebo group at the end of the study, the difference proved highly significant (p < 0.014). PSA measurements, maximal and average urinary flow rates, and residual volumes showed no statistically significant differences. When taken for 3 months, a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) compared to placebo can significantly lessen nocturia and frequency and diminish overall symptomatology of BPH as indicated by an improvement in the total AUA Symptom Index score. The combination of natural products caused no significant adverse side effects.

Successful closure of chronic BPF by thoracoscopy after failure of endoscopic fibrin glue application and thoracoplasty.

PubMed

Tschopp, J M; Evéquoz, D; Karrer, W; Aymon, E; Naef, A P

1990-03-01

We report a case of chronic debilitating BPF following right upper lobe resection. Despite several endobronchial applications of fibrin glue, we could not close it. Since the patient was extremely debilitated by symptoms due to the BPF, a thoracoplasty was attempted but was not successful. Finally, the BPF was definitely closed by instillation of talc into the pleura through thoracoscopy. To our knowledge, this is the first reported case of chemical closure of a recalcitrant BPF by the route of thoracoscopy. It also shows the failure of endoscopic fibrin glue application in such a condition.

Statistical Challenges in Biomedical Research

NASA Technical Reports Server (NTRS)

Feiveson, Alan H.; Ploutz-Snyder, Rob; Fiedler, James

2010-01-01

Potentially debilitating effects of spaceflight environment include: a) Bone Demineralization - Osteoporosis. b)Impaired Fracture Healing - Non-Union. c) Renal Stone Formation & Soft Tissue Calcification. d) Orthostatic Intolerance (on return to gravity). e) Cardiac Arrhythmias. f) Dehydration (on return to gravity). g) Decreased Aerobic Capacity. h) Impaired Coordination. i) Muscle Atrophy (Loss of Strength). j) Radiation Sickness. k) Increased Cancer Risk. l) Impaired Immune Function. m) Behavioral Changes & Performance Decrements n) Altitude Decompression Sickness during EVA.

Perceived benefits and barriers to exercise for recently treated patients with multiple myeloma: a qualitative study.

PubMed

Craike, Melinda J; Hose, Kaye; Courneya, Kerry S; Harrison, Simon J; Livingston, Patricia M

2013-07-01

Understanding the physical activity experiences of patients with multiple myeloma (MM) is essential to inform the development of evidence-based interventions and to quantify the benefits of physical activity. The aim of this study was to gain an in-depth understanding of the physical activity experiences and perceived benefits and barriers to physical activity for patients with MM. This was a qualitative study that used a grounded theory approach. Semi-structured interviews were conducted in Victoria, Australia by telephone from December 2011-February 2012 with patients who had been treated for MM within the preceding 2-12 months. Interviews were transcribed and analysed using the constant comparison coding method to reduce the data to themes. Gender differences and differences between treatment groups were explored. Twenty-four interviews were completed. The sample comprised 13 females (54%), with a mean age of 62 years (SD = 8.8). Sixteen (67%) participants had received an autologous stem cell transplant (ASCT). All participants currently engaged in a range of light to moderate intensity physical activity; walking and gardening were the most common activities. Recovery from the symptoms of MM and side effects of therapy, psychological benefits, social factors and enjoyment were important benefits of physical activity. Barriers to physical activity predominately related to the symptoms of MM and side effects of therapy, including pain, fatigue, and fear of infection. Low self- motivation was also a barrier. Women participated in a more diverse range of physical activities than men and there were gender differences in preferred type of physical activity. Women were more likely to report psychological and social benefits; whereas men reported physical activity as a way to keep busy and self-motivation was a barrier. Patients treated with an ASCT more often reported affective benefits of participation in physical activity and fatigue as a barrier. Patients treated with other therapies (e.g., chemotherapy, radiotherapy) were more likely to report pain as a barrier. Patients with MM experience debilitating effects of their condition and therapy, which influences their level and intensity of physical activity participation. Physical activity programs should be individualised; take into consideration gender differences and the impact of different types of therapy on physical activity; and focus on meeting the psychological, coping and recovery needs of patients.

Prism Adaptation Alters Electrophysiological Markers of Attentional Processes in the Healthy Brain.

PubMed

Martín-Arévalo, Elisa; Laube, Inga; Koun, Eric; Farnè, Alessandro; Reilly, Karen T; Pisella, Laure

2016-01-20

Neglect patients typically show a rightward attentional orienting bias and a strong disengagement deficit, such that they are especially slow in responding to left-sided targets after right-sided cues (Posner et al., 1984). Prism adaptation (PA) can reduce diverse debilitating neglect symptoms and it has been hypothesized that PA's effects are so generalized that they might be mediated by attentional mechanisms (Pisella et al., 2006; Redding and Wallace, 2006). In neglect patients, performance on spatial attention tasks improves after rightward-deviating PA (Jacquin-Courtois et al., 2013). In contrast, in healthy subjects, although there is evidence that leftward-deviating PA induces neglect-like performance on some visuospatial tasks, behavioral studies of spatial attention tasks have mostly yielded negative results (Morris et al., 2004; Bultitude et al., 2013). We hypothesized that these negative behavioral findings might reflect the limitations of behavioral measures in healthy subjects. Here we exploited the sensitivity of event-related potentials to test the hypothesis that electrophysiological markers of attentional processes in the healthy human brain are affected by PA. Leftward-deviating PA generated asymmetries in attentional orienting (reflected in the cue-locked N1) and in attentional disengagement for invalidly cued left targets (reflected in the target-locked P1). This is the first electrophysiological demonstration that leftward-deviating PA in healthy subjects mimics attentional patterns typically seen in neglect patients. Significance statement: Prism adaptation (PA) is a promising tool for ameliorating many deficits in neglect patients and inducing neglect-like behavior in healthy subjects. The mechanisms underlying PA's effects are poorly understood but one hypothesis suggests that it acts by modulating attention. To date, however, there has been no successful demonstration of attentional modulation in healthy subjects. We provide the first electrophysiological evidence that PA acts on attention in healthy subjects by mimicking the attentional pattern typically reported in neglect patients: both a rightward attentional orienting bias (reflected in the cue-locked N1) and a deficit in attentional disengagement from the right hemispace (reflected in the target-locked P1). This study makes an important contribution to refining current models of the mechanisms underlying PA's cognitive effects. Copyright © 2016 the authors 0270-6474/16/361019-12$15.00/0.

Contentious host-microbiota relationship in inflammatory bowel disease--can foes become friends again?

PubMed

Satokari, Reetta

2015-01-01

Inflammatory bowel diseases (IBDs) are chronic debilitating disorders of unknown etiology, consisting of two main conditions, ulcerative colitis and Crohn's disease. Major advances have recently taken place in human genetic studies of IBD and over 160 risk loci for these two diseases have been uncovered. These genetic data highlight a key role for genes that code for immunological and epithelial barrier functions. Environmental factors also make substantial contributions to the pathogenesis of IBD and account for the growing incidence of the diseases around the world. Intestinal microbiota creates resistance to infection, provides nutrients, and educates the immune system and in many ways has a significant impact on human health. Aberrant microbiota composition and decreased diversity (dysbiotic microbiota) are key etiopathological events in IBD. Dysbiotic microbiota can lead to loss of normal, regulatory immune effects in the gut mucosa. This may play a central role in the development and perpetuation of chronic inflammation. Further, the expression of specific innate immune receptors that recognize microbes is altered in the IBD epithelium. Therefore, the combination of host side epithelial barrier functions and the presence of dysbiotic microbiota in the gut together promote inflammation. New therapeutic options targeting microbiota are currently considered for IBD and they may, in the future, provide means to reverse the pathogenic host-microbiota relationship into a symbiotic one. In this review, the focus is on the intestinal microbiota and host-microbe interactions in IBD.

CAPTURE OF FREE-RANGING MULE DEER (ODOCOILEUS HEMIONUS) WITH A COMBINATION OF MEDETOMIDINE, AZAPERONE, AND ALFAXALONE.

PubMed

Mathieu, Amélie; Caulkett, Nigel; Stent, Patrick M; Schwantje, Helen M

2017-04-01

The combination of medetomidine, azaperone, and alfaxalone has been successfully used to anesthetize captive white-tailed deer ( Odocoileus virginianus ). This same combination was utilized to immobilize free-ranging female mule deer ( Odocoileus hemionus ; MD) in urban and nonurban environments (14 urban MD, 14 nonurban MD) in British Columbia, Canada. Physiologic data were collected to assess the safety and reliability of this drug combination under field conditions. Each deer received estimated dosages of 0.15 mg/kg medetomidine, 0.2 mg/kg azaperone, and 0.5 mg/kg alfaxalone intramuscularly via a remote darting system. Inductions were calm and rapid (mean time to sternal recumbency: urban MD, 6.4±2.2 min; nonurban MD, 8.2±4.1 min). Supplemental drugs were required to induce lateral recumbency in five deer, four of which had experienced initial dart failure (mean time to lateral recumbency: urban MD, 8.5±3.8 min; nonurban MD, 18.7±16.5 min). Recoveries were smooth and uneventful (time to standing: urban MD, 12.5±3.4 min; nonurban MD, 9.0±3.5 min) for all but one debilitated nonurban MD that died shortly after atipamezole administration (at five times the medetomidine dose). The major side effects of the combination were hypoxemia and hypercapnia. The combination of medetomidine, azaperone, and alfaxalone proved suitable for the immobilization of urban and nonurban free-ranging MD.

AR-v7 liquid biopsy for treatment stratification in prostate cancer: how close are we?

PubMed

Fletcher, Claire

2017-09-01

Recent clinical introduction of the novel antiandrogen, Enzalutamide (Enza), CYP17 inhibitor, Abiraterone (Abi), and the second-generation chemotherapeutic, Cabazitaxel, has increased survival of patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). However, de novo and acquired resistance rates are high. A liquid biopsy that can rapidly, sensitively and robustly identify which patients will respond to treatment in a minimally invasive manner is urgently required to permit switch to a potentially more efficacious drug regimen, thus increasing survival whilst avoiding debilitating side effects associated with unnecessary treatment. This review will highlight recent developments in detection of AR-v7 in circulating mRNA/whole blood and circulating tumour cells (CTCs) as a liquid biopsy for patient-stratification in mCRPC. Continued androgen receptor (AR) activity in mCRPC has been linked to the expression of a number of truncated but constitutively active AR isoforms. One such variant, AR-v7, can drive drug resistance in preclinical models and is correlated with disease progression whilst showing dynamic response to AR-targeting treatments when assessed in blood. It has thus been proposed as an Abi/Enza treatment-response biomarker. AR-v7 liquid biopsy has the potential to transform clinical management of mCRPC and increase patient survival. This review will explore recent efforts to validate AR-v7 as a robust, clinically informative biomarker. I will also address potential limitations of detection and quantification that could frustrate its adoption into routine clinical practise.

Provider perspectives on treatment decision-making in nephrotic syndrome.

PubMed

Hladunewich, Michelle A; Beanlands, Heather; Herreshoff, Emily; Troost, Jonathan P; Maione, Maria; Trachtman, Howard; Poulton, Caroline; Nachman, Patrick; Modes, Mary Margaret; Hailperin, Marilyn; Pitter, Renee; Gipson, Debbie S

2017-01-01

Managing patients with nephrotic syndrome (NS) remains difficult for the practicing nephrologist. This often young patient population is faced with a debilitating, relapsing and remitting disease with non-specific treatment options that are often poorly tolerated. Clinicians managing these complex patients must attempt to apply disease-specific evidence while considering the individual patient's clinical and personal situation. We conducted qualitative interviews to ascertain the provider perspectives of NS, treatment options and factors that influence recommendations for disease management, and administered a survey to assess both facilitators and barriers to the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. When making treatment recommendations, providers considered characteristics of various treatments such as efficacy, side effects and evaluation of risk versus benefit, taking into account how the specific treatment fit with the individual patient. Time constraints and the complexity of explaining the intricacies of NS were noted as significant barriers to care. Although the availability of guidelines was deemed a facilitator to care, the value of the KDIGO guidelines was limited by the perception of poor quality of evidence. The complexity of NS and the scarcity of robust evidence to support treatment recommendations are common challenges reported by nephrologists. Future development and use of shared learning platforms may support the integration of best available evidence, patient/family preferences and exchange of information at a pace that is unconstrained by the outpatient clinic schedule. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The Glutamatergic Aspects of Schizophrenia Molecular Pathophysiology: Role of the Postsynaptic Density, and Implications for Treatment

PubMed Central

Iasevoli, Felice; Tomasetti, Carmine; Buonaguro, Elisabetta F.; de Bartolomeis, Andrea

2014-01-01

Schizophrenia is one of the most debilitating psychiatric diseases with a lifetime prevalence of approximately 1%. Although the specific molecular underpinnings of schizophrenia are still unknown, evidence has long linked its pathophysiology to postsynaptic abnormalities. The postsynaptic density (PSD) is among the molecular structures suggested to be potentially involved in schizophrenia. More specifically, the PSD is an electron-dense thickening of glutamatergic synapses, including ionotropic and metabotropic glutamate receptors, cytoskeletal and scaffolding proteins, and adhesion and signaling molecules. Being implicated in the postsynaptic signaling of multiple neurotransmitter systems, mostly dopamine and glutamate, the PSD constitutes an ideal candidate for studying dopamine-glutamate disturbances in schizophrenia. Recent evidence suggests that some PSD proteins, such as PSD-95, Shank, and Homer are implicated in severe behavioral disorders, including schizophrenia. These findings, further corroborated by genetic and animal studies of schizophrenia, offer new insights for the development of pharmacological strategies able to overcome the limitations in terms of efficacy and side effects of current schizophrenia treatment. Indeed, PSD proteins are now being considered as potential molecular targets against this devastating illness. The current paper reviews the most recent hypotheses on the molecular mechanisms underlying schizophrenia pathophysiology. First, we review glutamatergic dysfunctions in schizophrenia and we provide an update on postsynaptic molecules involvement in schizophrenia pathophysiology by addressing both human and animal studies. Finally, the possibility that PSD proteins may represent potential targets for new molecular interventions in psychosis will be discussed. PMID:24851087

Nicotinic receptors as CNS targets for Parkinson's disease.

PubMed

Quik, Maryka; Bordia, Tanuja; O'Leary, Kathryn

2007-10-15

Parkinson's disease is a debilitating neurodegenerative movement disorder characterized by damage to the nigrostriatal dopaminergic system. Current therapies are symptomatic only and may be accompanied by serious side effects. There is therefore a continual search for novel compounds for the treatment of Parkinson's disease symptoms, as well as to reduce or halt disease progression. Nicotine administration has been reported to improve motor deficits that arise with nigrostriatal damage in parkinsonian animals and in Parkinson's disease. In addition, nicotine protects against nigrostriatal damage in experimental models, findings that have led to the suggestion that the reduced incidence of Parkinson's disease in smokers may be due to the nicotine in tobacco. Altogether, these observations suggest that nicotine treatment may be beneficial in Parkinson's disease. Nicotine interacts with multiple nicotinic receptor (nAChR) subtypes in the peripheral and central nervous system, as well as in skeletal muscle. Work to identify the subtypes affected in Parkinson's disease is therefore critical for the development of targeted therapies. Results show that striatal alpha6beta2-containing nAChRs are particularly susceptible to nigrostriatal damage, with a decline in receptor levels that closely parallels losses in striatal dopamine. In contrast, alpha4beta2-containing nAChRs are decreased to a much smaller extent under the same conditions. These observations suggest that development of nAChR agonists or antagonists targeted to alpha6beta2-containing nAChRs may represent a particularly relevant target for Parkinson's disease therapeutics.

Depression in the classroom: considerations and strategies.

PubMed

Calear, Alison L

2012-01-01

Depression is a prevalent and debilitating disorder that can severely affect a young person’s social, emotional, and academic functioning. Identifying depression early is essential to reducing the impact of this disorder. Depression is treatable. However, there are a number of classroom and school supports that can be put in place to assist a young person experiencing or recovering from depression. Preventing the development of depression through effective classroom programs should be encouraged and supported within the school environment.

Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation

DTIC Science & Technology

2015-10-01

currently investigating the effects of CG stimulation in subjects with debilitating pain due to cervical or thoracic SCI. This study stemmed from...had a low thoracic injury and pain in lumbar dermatomes, whereas Subject 1 had mainly mid- cervical pain that responded minimally to DBS and matched...AWARD NUMBER: W81XWH-12-1-0559 TITLE: Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation PRINCIPAL

"If God wills...next year I will send her back to school": The Effects of Child and Parental Illness on School Participation in Rural Ethiopia. CREATE Pathways to Access. Research Monograph No. 60

ERIC Educational Resources Information Center

Orkin, Kate

2011-01-01

Rural Ethiopian children, and members of their households, often suffer from common and preventable but debilitating illnesses, such as malaria, parasite infection and worms. Enrolment rates in Ethiopia are high, but school attendance is patchy, children often drop out of school (although they sometimes return), and grade repetition is common.…

Diagnosis and treatment of academic frustration syndrome.

PubMed

Grover, P L; Tessier, K E

1978-09-01

A random sample of medical students was compared with others who were unable to cope with unanticipated academic frustration. The noncoping students demonstrated higher levels of debilitating anxiety and lower levels of facilitating anxiety while their perceptions of locus of control tended to be more extreme. No difference was found in study habits and attitudes. Techniques of attribution therapy and desensitization in the counseling of these students proved to be effective in improving coping behavior in six of seven cases.

Identification and Characterization of New Chemical Entities Targeting Apurinic/Apyrimidinic Endonuclease 1 for the Prevention of Chemotherapy-Induced Peripheral Neuropathy.

PubMed

Kelley, Mark R; Wikel, James H; Guo, Chunlu; Pollok, Karen E; Bailey, Barbara J; Wireman, Randy; Fishel, Melissa L; Vasko, Michael R

2016-11-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a potentially debilitating side effect of a number of chemotherapeutic agents. There are currently no U.S. Food and Drug Administration-approved interventions or prevention strategies for CIPN. Although the cellular mechanisms mediating CIPN remain to be determined, several lines of evidence support the notion that DNA damage caused by anticancer therapies could contribute to the neuropathy. DNA damage in sensory neurons after chemotherapy correlates with symptoms of CIPN. Augmenting apurinic/apyrimidinic endonuclease (APE)-1 function in the base excision repair pathway reverses this damage and the neurotoxicity caused by anticancer therapies. This neuronal protection is accomplished by either overexpressing APE1 or by using a first-generation targeted APE1 small molecule, E3330 [(2E)-2-[(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)methylene]-undecanoic acid; also called APX3330]. Although E3330 has been approved for phase 1 clinical trials (Investigational New Drug application number IND125360), we synthesized novel, second-generation APE1-targeted molecules and determined whether they would be protective against neurotoxicity induced by cisplatin or oxaliplatin while not diminishing the platins' antitumor effect. We measured various endpoints of neurotoxicity using our ex vivo model of sensory neurons in culture, and we determined that APX2009 [(2E)-2-[(3-methoxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)methylidene]-N,N-diethylpentanamide] is an effective small molecule that is neuroprotective against cisplatin and oxaliplatin-induced toxicity. APX2009 also demonstrated a strong tumor cell killing effect in tumor cells and the enhanced tumor cell killing was further substantiated in a more robust three-dimensional pancreatic tumor model. Together, these data suggest that the second-generation compound APX2009 is effective in preventing or reversing platinum-induced CIPN while not affecting the anticancer activity of platins. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

EGCG debilitates the persistence of EBV latency by reducing the DNA binding potency of nuclear antigen 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Ya-Lin; Tsai, Hsing-Lyn; Peng, Chih-Wen, E-mail: pengcw@mail.tcu.edu.tw

Highlights: Black-Right-Pointing-Pointer Two cell-based reporter platforms were established for screening of EBNA1 inhibitors. Black-Right-Pointing-Pointer EGCG acts as an inhibitor to block EBNA1 binding with the cognate oriP sequence. Black-Right-Pointing-Pointer EGCG debilitates EBNA1-dependent transcription enhancement and episome maintenance. Black-Right-Pointing-Pointer EGCG impairs persistence of EBV latency. Black-Right-Pointing-Pointer EGCG is a potent anti-EBV agent for targeting the latent cascade of EBV. -- Abstract: Because the expression of EBNA1 is prevalent in all EBV-associated tumors, it has become one of the most attractive drug targets for the discovery of anti-EBV compounds. In a cell-based reporter system, EBNA1 consistently upregulated the transcription of an oriP-Lucmore » mini-EBV episome by 6- to 8-fold. The treatment of cells with 50 {mu}M EGCG effectively blocked the binding of EBNA1 to oriP-DNA both in vivo and in vitro, which led to the abrogation of EBNA1-dependent episome maintenance and transcriptional enhancement. Importantly, the anti-EBNA1 effects caused by EGCG ultimately impaired the persistence of EBV latent infection. Our data suggest that the inhibition of EBNA1 activity by EGCG could be a promising starting point for the development of new protocols for anti-EBV therapy.« less

Goofy vs. Regular: Laterality effects in surfing.

PubMed

Furley, Philip; Dörr, Jannik; Loffing, Florian

2018-02-01

The aim of the present study was to test if lateral preferences of surfers are associated with behaviour and performance depending on the direction of a breaking wave. We hypothesized that wave direction and surf stance interact in creating favourable or debilitative performance demands as surfers are either facing the wave (frontside) or the wave is breaking in the back of the surfers (backside). Study 1 was an online survey collecting self-report data of recreational surfers (n = 394). In Study 2, we analysed all wave scores (n = 2,552) and laterality of professional surfers during the season of 2014. Study 1 demonstrated that recreational surfers preferred surfing frontside and described themselves as more skilful when surfing frontside as this is facilitative for picking up visual information. Study 2 did not provide clear evidence that professional surfers on average scored higher during contests when surfing frontside, but when professional surfers had a choice of surfing frontside vs. backside, they were more likely to surf frontside. We discuss the diverging findings between Study 1 and Study 2 from the "circumvention-of-limits" argumentation within the expertise literature as professional surfers most likely have acquired skills allowing them to compensate for debilitative individual and environmental circumstances.

Testing the odontocete acoustic prey debilitation hypothesis: no stunning results.

PubMed

Benoit-Bird, Kelly J; Au, Whitlow W L; Kastelein, Ronald

2006-08-01

The hypothesis that sounds produced by odontocetes can debilitate fish was examined. The effects of simulated odontocete pulsed signals on three species of fish commonly preyed on by odontocetes were examined, exposing three individuals of each species as well as groups of four fish to a high-frequency click of a bottlenose dolphin [peak frequency (PF) 120 kHz, 213-dB peak-to-peak exposure level (EL)], a midfrequency click modeled after a killer whale's signal (PF 55 kHz, 208-dB EL), and a low-frequency click (PF 18 kHz, 193-dB EL). Fish were held in a 50-cm diameter net enclosure immediately in front of a transducer where their swimming behavior, orientation, and balance were observed with two video cameras. Clicks were presented at constant rates and in graded sweeps simulating a foraging dolphin's "terminal buzz." No measurable change in behavior was observed in any of the fish for any signal type or pulse modulation rate, despite the fact that clicks were at or near the maximum source levels recorded for odontocetes. Based on the results, the hypothesis that acoustic signals of odontocetes alone can disorient or "stun" prey cannot be supported.

Oropharyngeal dysphagia pathophysiology, complications and science-based interventions.

PubMed

Altman, Kenneth W

2012-01-01

The etiology of oropharyngeal dysphagia can be broad, and includes aging with atrophy, debilitation, stroke, neurodegenerative and muscular diseases, tumor and postsurgical deformity, as well as effects due to medications and drying of the mucosal membranes. Pathophysiology depends on the multiple causative factors, including the cortex and neural connections to generate the swallow, as well as the oropharyngeal musculature. While chronic debilitation and age may result in nutritional deficiency and poor hydration, the other causes generally present with aspiration risk more acutely. Bacteriologically, aspiration pneumonia is usually polymicrobial with a predominance of Gram-negative enteric bacilli. However, there is emerging evidence to suggest that odontogenic sources may complicate the severity of bacterial load. The principles behind science-based interventions are primarily aspiration assessment with bedside evaluation, and ultimately modified barium swallow (videofluoroscopy) or functional endoscopic evaluation of swallowing (with or without sensory testing). Each has its advantages and logistical concerns. Intervention and rehabilitation is unique to the patient's needs, but may include reconditioning and therapy with a speech and language pathologist, and surgical options. The emerging roles of neuroplasticity and external neuromuscular stimulation are also discussed. Copyright © 2012 S. Karger AG, Basel.

An Audit of the Use of Gonadorelin Analogues to Prevent Recurrent Acute Symptoms in Patients with Acute Porphyria in the United Kingdom.

PubMed

Schulenburg-Brand, Danja; Gardiner, Tricia; Guppy, Simon; Rees, David C; Stein, Penelope; Barth, Julian; Felicity Stewart, M; Badminton, Michael

2017-01-01

Severe recurrent acute attacks of porphyria have traditionally been treated with either prophylactic human haemin or gonadorelin analogues (GnA) in females. Evidence on the most effective treatment for this patient subgroup is lacking. This audit surveyed the use of prophylactic GnA in the UK.Twenty female patients (who experienced between 2 and 45 acute attacks of porphyria requiring hospitalisation and treatment with human haemin prior to GnA prophylaxis) were included in the audit. Data was retrospectively collected based on patient history and case review.Twenty three treatment courses were given lasting a median period of 12 months. Monthly subcutaneous Goserelin was most commonly used. In three patients in whom timing with the menstrual cycle was not considered, an acute attack occurred after initiation of the first dose. The majority of patients experienced oestrogen deficiency symptoms during treatment. Fifty percent of the prescribed courses of GnA resulted in a degree of clinical benefit. This successfully treated group experienced between 3 and 20 acute attacks prior to and between 0 and 6 acute attacks during GnA treatment.The audit revealed large variation in practice in the United Kingdom regarding indication, duration of treatment, specific drug used and management of side effects. In view of the limited treatment options available for this cohort and the mixed outcome successes reported, we believe it is reasonable for porphyria specialists to continue offering GnA treatment to women with severe recurrent debilitating acute attacks of porphyria associated with the menstrual cycle, and we propose best practice guidelines to standardise management.

MitoPark mice, an animal model of Parkinson's disease, show enhanced prepulse inhibition of acoustic startle and no loss of gating in response to the adenosine A(2A) antagonist SCH 412348.

PubMed

Grauer, Steven M; Hodgson, Robert; Hyde, Lynn A

2014-04-01

Psychoses are debilitating side effects associated with current dopaminergic treatments for Parkinson's disease (PD). Prepulse inhibition (PPI), in which a non-startling stimulus reduces startle response to a subsequent startle-eliciting stimulus, is important in filtering out extraneous sensory stimuli. PPI deficits induced by dopamine agonists can model symptoms of psychosis. Adenosine A(2A) receptor antagonists, being developed as novel PD treatments, indirectly modulate dopamine signaling in the basal ganglia and may have an improved psychosis profile which could be detected using the PPI model. The aims of this study is to characterize PPI in MitoPark mice, which exhibit progressive loss of dopamine signaling and develop a Parkinson-like motor phenotype, and assess standard and novel PD treatment effects on PPI in MitoPark mice, which more closely mimic the basal ganglia dopamine status of PD patients. MitoPark mice displayed enhanced PPI as dopamine tone decreased with age, consistent with studies in intact mice that show enhanced PPI in response to dopamine antagonists. Paradoxically, older MitoParks were more sensitive to PPI disruption when challenged with dopamine agonists such as apomorphine or pramipexole. Alternatively, SCH 412348, an adenosine A(2A) antagonist, did not disrupt PPI in MitoPark mice at doses that normalized hypoactivity. Use of MitoPark mice in the PPI assay to assess the potential for PD treatment to produce psychoses likely represents a more disease-relevant model. SCH 412348 does not differentially disrupt PPI as do dopamine agonists, perhaps indicative of an improved psychosis profile of adenosine A(2A) antagonists, even in PD patients with decreased dopamine tone in the basal ganglia.

Experimentally Dissecting the Origins of Peroxiredoxin Catalysis.

PubMed

Nelson, Kimberly J; Perkins, Arden; Van Swearingen, Amanda E D; Hartman, Steven; Brereton, Andrew E; Parsonage, Derek; Salsbury, Freddie R; Karplus, P Andrew; Poole, Leslie B

2018-03-01

Peroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidases involved in oxidant defense and signal transduction. Despite much study, the precise roles of conserved residues remain poorly defined. In this study, we carried out extensive functional and structural characterization of 10 variants of such residues in a model decameric bacterial Prx. Three active site proximal mutations of Salmonella typhimurium AhpC, T43V, R119A, and E49Q, lowered catalytic efficiency with hydrogen peroxide by 4-5 orders of magnitude, but did not affect reactivity toward their reductant, AhpF. pK a values of the peroxidatic cysteine were also shifted up by 1-1.3 pH units for these and a decamer disruption mutant, T77I. Except for the decamer-stabilizing T77V, all mutations destabilized decamers in the reduced form. In the oxidized form, three mutants-T77V, T43A, and T43S-exhibited stabilized decamers and were more efficiently reduced by AhpF than wild-type AhpC. Crystal structures of most mutants were solved and many showed alterations in stability of the fully folded active site loop. This is the first study of Prx mutants to comprehensively assess the effects of mutations on catalytic activities, the active site cysteine pK a , and the protein structure and oligomeric status. The Arg119 side chain must be properly situated for efficient catalysis, but for other debilitating variants, the functional defects could be explained by structural perturbations and/or associated decamer destabilization rather than direct effects. This underscores the importance of our comprehensive approach. A remarkable new finding was the preference of the reductant for decamers. Antioxid. Redox Signal. 28, 521-536.

Vagus nerve stimulation improves locomotion and neuronal populations in a model of Parkinson's disease.

PubMed

Farrand, Ariana Q; Helke, Kristi L; Gregory, Rebecca A; Gooz, Monika; Hinson, Vanessa K; Boger, Heather A

Parkinson's disease (PD) is a progressive, neurodegenerative disorder with no disease-modifying therapies, and symptomatic treatments are often limited by debilitating side effects. In PD, locus coeruleus noradrenergic (LC-NE) neurons degenerate prior to substantia nigra dopaminergic (SN-DA) neurons. Vagus nerve stimulation (VNS) activates LC neurons, and decreases pro-inflammatory markers, allowing improvement of LC targets, making it a potential PD therapeutic. To assess therapeutic potential of VNS in a PD model. To mimic the progression of PD degeneration, rats received a systemic injection of noradrenergic neurotoxin DSP-4, followed one week later by bilateral intrastriatal injection of dopaminergic neurotoxin 6-hydroxydopamine. At this time, a subset of rats also had vagus cuffs implanted. After eleven days, rats received a precise VNS regimen twice a day for ten days, and locomotion was measured during each afternoon session. Immediately following final stimulation, rats were euthanized, and left dorsal striatum, bilateral SN and LC were sectioned for immunohistochemical detection of monoaminergic neurons (tyrosine hydroxylase, TH), α-synuclein, astrocytes (GFAP) and microglia (Iba-1). VNS significantly increased locomotion of lesioned rats. VNS also resulted in increased expression of TH in striatum, SN, and LC; decreased SN α-synuclein expression; and decreased expression of glial markers in the SN and LC of lesioned rats. Additionally, saline-treated rats after VNS, had higher LC TH and lower SN Iba-1. Our findings of increased locomotion, beneficial effects on LC-NE and SN-DA neurons, decreased α-synuclein density in SN TH-positive neurons, and neuroinflammation suggest VNS has potential as a novel PD therapeutic. Copyright © 2017 Elsevier Inc. All rights reserved.

Screening for AMPA receptor auxiliary subunit specific modulators

PubMed Central

Azumaya, Caleigh M.; Days, Emily L.; Vinson, Paige N.; Stauffer, Shaun; Sulikowski, Gary; Weaver, C. David; Nakagawa, Terunaga

2017-01-01

AMPA receptors (AMPAR) are ligand gated ion channels critical for synaptic transmission and plasticity. Their dysfunction is implicated in a variety of psychiatric and neurological diseases ranging from major depressive disorder to amyotrophic lateral sclerosis. Attempting to potentiate or depress AMPAR activity is an inherently difficult balancing act between effective treatments and debilitating side effects. A newly explored strategy to target subsets of AMPARs in the central nervous system is to identify compounds that affect specific AMPAR-auxiliary subunit complexes. This exploits diverse spatio-temporal expression patterns of known AMPAR auxiliary subunits, providing means for designing brain region-selective compounds. Here we report a high-throughput screening-based pipeline that can identify compounds that are selective for GluA2-CNIH3 and GluA2-stargazin complexes. These compounds will help us build upon the growing library of AMPAR-auxiliary subunit specific inhibitors, which have thus far all been targeted to TARP γ-8. We used a cell-based assay combined with a voltage-sensitive dye (VSD) to identify changes in glutamate-gated cation flow across the membranes of HEK cells co-expressing GluA2 and an auxiliary subunit. We then used a calcium flux assay to further validate hits picked from the VSD assay. VU0612951 and VU0627849 are candidate compounds from the initial screen that were identified as negative and positive allosteric modulators (NAM and PAM), respectively. They both have lower IC50/EC50s on complexes containing stargazin and CNIH3 than GSG1L or the AMPAR alone. We have also identified a candidate compound, VU0539491, that has NAM activity in GluA2(R)-CNIH3 and GluA2(Q) complexes and PAM activity in GluA2(Q)-GSG1L complexes. PMID:28358902

Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

PubMed

Peron, Jean Pierre Schatzmann; de Brito, Auriléia Aparecida; Pelatti, Mayra; Brandão, Wesley Nogueira; Vitoretti, Luana Beatriz; Greiffo, Flávia Regina; da Silveira, Elaine Cristina; Oliveira-Junior, Manuel Carneiro; Maluf, Mariangela; Evangelista, Lucila; Halpern, Silvio; Nisenbaum, Marcelo Gil; Perin, Paulo; Czeresnia, Carlos Eduardo; Câmara, Niels Olsen Saraiva; Aimbire, Flávio; Vieira, Rodolfo de Paula; Zatz, Mayana; de Oliveira, Ana Paula Ligeiro

2015-01-01

Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke–Induced COPD in C57BL/6 mice

PubMed Central

Peron, Jean Pierre Schatzmann; de Brito, Auriléia Aparecida; Pelatti, Mayra; Brandão, Wesley Nogueira; Vitoretti, Luana Beatriz; Greiffo, Flávia Regina; da Silveira, Elaine Cristina; Oliveira-Junior, Manuel Carneiro; Maluf, Mariangela; Evangelista, Lucila; Halpern, Silvio; Nisenbaum, Marcelo Gil; Perin, Paulo; Czeresnia, Carlos Eduardo; Câmara, Niels Olsen Saraiva; Aimbire, Flávio; Vieira, Rodolfo de Paula; Zatz, Mayana; Ligeiro de Oliveira, Ana Paula

2015-01-01

Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J—660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD. PMID:26322981

TAT-Mediated Delivery of Tousled Protein to Salivary Glands Protects Against Radiation-Induced Hypofunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sunavala-Dossabhoy, Gulshan, E-mail: gsunav@lsuhsc.edu; Palaniyandi, Senthilnathan; Richardson, Charles

2012-09-01

Purpose: Patients treated with radiotherapy for head-and-neck cancer invariably suffer its deleterious side effect, xerostomia. Salivary hypofunction ensuing from the irreversible destruction of glands is the most common and debilitating oral complication affecting patients undergoing regional radiotherapy. Given that the current management of xerostomia is palliative and ineffective, efforts are now directed toward preventive measures to preserve gland function. The human homolog of Tousled protein, TLK1B, facilitates chromatin remodeling at DNA repair sites and improves cell survival against ionizing radiation (IR). Therefore, we wanted to determine whether a direct transfer of TLK1B protein to rat salivary glands could protect againstmore » IR-induced salivary hypofunction. Methods: The cell-permeable TAT-TLK1B fusion protein was generated. Rat acinar cell line and rat salivary glands were pretreated with TAT peptide or TAT-TLK1B before IR. The acinar cell survival in vitro and salivary function in vivo were assessed after radiation. Results: We demonstrated that rat acinar cells transduced with TAT-TLK1B were more resistant to radiation (D{sub 0} = 4.13 {+-} 1.0 Gy; {alpha}/{beta} = 0 Gy) compared with cells transduced with the TAT peptide (D{sub 0} = 4.91 {+-} 1.0 Gy; {alpha}/{beta} = 20.2 Gy). Correspondingly, retroductal instillation of TAT-TLK1B in rat submandibular glands better preserved salivary flow after IR (89%) compared with animals pretreated with Opti-MEM or TAT peptide (31% and 39%, respectively; p < 0.01). Conclusions: The results demonstrate that a direct transfer of TLK1B protein to the salivary glands effectively attenuates radiation-mediated gland dysfunction. Prophylactic TLK1B-protein therapy could benefit patients undergoing radiotherapy for head-and-neck cancer.« less

The role of TRAIL in fatigue induced by repeated stress from radiotherapy.

PubMed

Feng, Li Rebekah; Suy, Simeng; Collins, Sean P; Saligan, Leorey N

2017-08-01

Fatigue is one of the most common and debilitating side effects of cancer and cancer treatment, and yet its etiology remains elusive. The goal of this study is to understand the role of chronic inflammation in fatigue following repeated stress from radiotherapy. Fatigue and non-fatigue categories were assessed using ≥ 3-point change in Functional Assessment of Cancer Therapy-Fatigue questionnaire (FACT-F) administered to participants at baseline/before radiotherapy and one year post-radiotherapy. Whole genome microarray and cytokine multiplex panel were used to examine fatigue-related transcriptome and serum cytokine changes, respectively. The study included 86 subjects (discovery phase n = 40, validation phase n = 46). The sample in the discovery phase included men with prostate cancer scheduled to receive external-beam radiotherapy. A panel of 48 cytokines were measured and the significantly changed cytokine found in the discovery phase was validated using sera from a separate cohort of men two years after completing radiotherapy for prostate cancer at a different institution. Effects of the significantly changed cytokine on cell viability was quantified using the MTT assay. During the discovery phase, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL decoy receptor, TNFRSF10C (TRAIL-R3), were significantly upregulated in fatigued (≥3-point decrease from baseline to 1yr-post radiotherapy) subjects (n = 15). In the validation phase, TRAIL correlated with fatigue scores 2yrs post-radiotherapy. TRAIL caused selective cytotoxicity in neuronal cells, but not in microglial and muscle cells, in vitro. Late-onset inflammation directed by TRAIL may play a role in fatigue pathogenesis post-repeated stress from irradiation. Published by Elsevier Ltd.

Living with Ankylosing Spondylitis: the patient's perspective.

PubMed

Hamilton-West, Kate E; Quine, Lyn

2009-09-01

Ankylosing Spondylitis (AS) is a potentially debilitating chronic condition that necessitates a biopsychosocial approach for successful long-term management. However, the psychosocial consequences of AS are not well understood. In this study patients (N = 68) reported impacts of AS across a wide range of life domains; negative impacts included physical effects of AS, changes in mood or personality, effects on social life and relationships with friends and family, low self-esteem, stigma and worry about the future; positive impacts included increased exercise, feelings of achievement and empathy, stronger relationships, slower pace of life and a more positive perspective. Implications for treatment are discussed.

Importance of Virtual Reality to Virtual Reality Exposure Therapy, Study Design of a Randomized Trial.

PubMed

McLay, Robert N; Baird, Alicia; Murphy, Jennifer; Deal, William; Tran, Lily; Anson, Heather; Klam, Warren; Johnston, Scott

2015-01-01

Post Traumatic Stress Disorder (PTSD) can be a debilitating problem in service members who have served in Iraq or Afghanistan. Virtual Reality Exposure Therapy (VRET) is one of the few interventions demonstrated in randomized controlled trials to be effective for PTSD in this population. There are theoretical reasons to expect that Virtual Reality (VR) adds to the effectiveness of exposure therapy, but there is also added expense and difficulty in using VR. Described is a trial comparing outcomes from VRET and a control exposure therapy (CET) protocol in service members with PTSD.

Benefits of aerobic exercise after stroke.

PubMed

Potempa, K; Braun, L T; Tinknell, T; Popovich, J

1996-05-01

The debilitating loss of function after a stroke has both primary and secondary effects on sensorimotor function. Primary effects include paresis, paralysis, spasticity, and sensory-perceptual dysfunction due to upper motor neuron damage. Secondary effects, contractures and disuse muscle atrophy, are also debilitating. This paper presents theoretical and empirical benefits of aerobic exercise after stroke, issues relevant to measuring peak capacity, exercise training protocols, and the clinical use of aerobic exercise in this patient population. A stroke, and resulting hemiparesis, produces physiological changes in muscle fibres and muscle metabolism during exercise. These changes, along with comorbid cardiovascular disease, must be considered when exercising stroke patients. While few studies have measured peak exercise capacity in hemiparetic populations, it has been consistently observed in these studies that stroke patients have a lower functional capacity than healthy populations. Hemiparetic patients have low peak exercise responses probably due to a reduced number of motor units available for recruitment during dynamic exercise, the reduced oxidative capacity of paretic muscle, and decreased overall endurance. Consequently, traditional methods to predict aerobic capacity are not appropriate for use with stroke patients. Endurance exercise training is increasingly recognised as an important component in rehabilitation. An average improvement in maximal oxygen consumption (VO2max) of 13.3% in stroke patients who participated in a 10-week aerobic exercise training programme has been reported compared with controls. This study underscored the potential benefits of aerobic exercise training in stroke patients. In this paper, advantages and disadvantages of exercise modalities are discussed in relation to stroke patients. Recommendations are presented to maximise physical performance and minimise potential cardiac risks during exercise.

The role of stress mindset in shaping cognitive, emotional, and physiological responses to challenging and threatening stress.

PubMed

Crum, Alia J; Akinola, Modupe; Martin, Ashley; Fath, Sean

2017-07-01

Prior research suggests that altering situation-specific evaluations of stress as challenging versus threatening can improve responses to stress. The aim of the current study was to explore whether cognitive, physiological and affective stress responses can be altered independent of situation-specific evaluations by changing individuals' mindsets about the nature of stress in general. Using a 2 × 2 design, we experimentally manipulated stress mindset using multi-media film clips orienting participants (N = 113) to either the enhancing or debilitating nature of stress. We also manipulated challenge and threat evaluations by providing positive or negative feedback to participants during a social stress test. Results revealed that under both threat and challenge stress evaluations, a stress-is-enhancing mindset produced sharper increases in anabolic ("growth") hormones relative to a stress-is-debilitating mindset. Furthermore, when the stress was evaluated as a challenge, a stress-is-enhancing mindset produced sharper increases in positive affect, heightened attentional bias towards positive stimuli, and greater cognitive flexibility, whereas a stress-is-debilitating mindset produced worse cognitive and affective outcomes. These findings advance stress management theory and practice by demonstrating that a short manipulation designed to generate a stress-is-enhancing mindset can improve responses to both challenging and threatening stress.

Training-as-treatment: effectiveness of the Certified Compassion Fatigue Specialist Training.

PubMed

Gentry, J Eric; Baggerly, Jennifer; Baranowsky, Anna

2004-01-01

Mental health and other service professionals who work with trauma survivors often experience the debilitating effects of compassion fatigue and caregiver stress. Leaders within the field have called for effective, empirically supported interventions for professionals who experience these negative effects. In response to the call, this study examines the treatment effectiveness of the Certified Compassion Fatigue Specialist Training (CCFST) for 83 participating mental health professionals. Results show a statistically and clinically significant decrease in participants' compassion fatigue and burnout symptoms and increase in their compassion satisfaction. A "training-as-treatment" effect of CCFST is introduced, described, and evaluated. Discussion of these findings, clinical implications, limitations, and future directions are provided. CCFST appears to be an effective intervention for ameliorating compassion fatigue symptoms in mental health professionals.

A Review on the Possible Neuroprotective Effects of Moringa Oleifera Leaf Extract.

PubMed

Igado, O O; Olopade, J O

2017-03-06

Moringa oleifera is an edible plant that has been reputed to be a miracle plant by numerous authors, with effects on practically every body system. Phytochemical analyses have demonstrated that the leaves are rich in various minerals, vitamins and antioxidants. Its use in some continents dates back to Antiquity. Neurodegeneration are chronic diseases of the nervous system. There is currently an increase in the use of natural products to combat these debilitating diseases. So far, no suitable cure has been found, and conditions are managed and the symptoms treated. This article reviews the literature on the effects of Moringa oleifera leaves on the nervous system in vivo and in vitro.

No blank slates: Pre-existing schemas about pharmaceuticals predict memory for side effects.

PubMed

Heller, Monika K; Chapman, Sarah C E; Horne, Rob

2017-04-01

Attribution of symptoms as medication side effects is informed by pre-existing beliefs about medicines and perceptions of personal sensitivity to their effects (pharmaceutical schemas). We tested whether (1) pharmaceutical schemas were associated with memory (recall/recognition) for side effect information (2) memory explained the attribution of a common unrelated symptom as a side effect. In this analogue study participants saw the patient leaflet of a fictitious asthma drug listing eight side effects. We measured recall and recognition memory for side effects and used a vignette to test whether participants attributed an unlisted common symptom (headache) as a side effect. Participants who perceived pharmaceuticals as more harmful in general recalled fewer side effects correctly (r Correct Recall  = -.273), were less able to differentiate between listed and unlisted side effects (r Recognition Sensitivity  = -.256) and were more likely to attribute the unlisted headache symptom as a side effect (r side effect attribution  = .381, ps < .01). The effect of harm beliefs on side effect attribution was partially mediated by correct recall of side effects. Pharmaceutical schemas are associated with memory for side effect information. Memory may explain part of the association between pharmaceutical schemas and the attribution of unrelated symptoms as side effects.

The Chicken or the Egg? The Direction of the Relationship Between Mathematics Anxiety and Mathematics Performance.

PubMed

Carey, Emma; Hill, Francesca; Devine, Amy; Szücs, Dénes

2015-01-01

This review considers the two possible causal directions between mathematics anxiety (MA) and poor mathematics performance. Either poor maths performance may elicit MA (referred to as the Deficit Theory), or MA may reduce future maths performance (referred to as the Debilitating Anxiety Model). The evidence is in conflict: the Deficit Theory is supported by longitudinal studies and studies of children with mathematical learning disabilities, but the Debilitating Anxiety Model is supported by research which manipulates anxiety levels and observes a change in mathematics performance. It is suggested that this mixture of evidence might indicate a bidirectional relationship between MA and mathematics performance (the Reciprocal Theory), in which MA and mathematics performance can influence one another in a vicious cycle.

Surgical treatment of Peyronie's disease.

PubMed

Carson, Culley C

2006-02-01

Peyronie's disease is a sexually debilitating disease causing significant penile deformity and erectile dysfunction as well as psychological stress for many men. The incidence of Peyronie's disease appears to be increasing and urologists are being called upon more frequently to treat this debilitating condition. Urologists have an opportunity to help men suffering from Peyronie's disease to improve their lives and the lives of their partners. Appropriate treatment should be individualized and tailored to the patient's expectations, disease history, physical exam findings, and coital function. After medical therapy is considered and the Peyronie's disease has stabilized, surgical correction is an excellent option for patients with functional impairment from their Peyronie's disease. Surgical outcomes are excellent with expected return to normal sexual function following Peyronie's disease treatment.

Ankylosing spondylitis: A state of the art factual backbone

PubMed Central

Ghasemi-rad, Mohammad; Attaya, Hosam; Lesha, Emal; Vegh, Andrea; Maleki-Miandoab, Tooraj; Nosair, Emad; Sepehrvand, Nariman; Davarian, Ali; Rajebi, Hamid; Pakniat, Abdolghader; Fazeli, Seyed Amirhossein; Mohammadi, Afshin

2015-01-01

Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects 1% of the general population. As one of the most severe types of spondyloarthropathy, AS affects the spinal vertebrae and sacroiliac joints, causing debilitating pain and loss of mobility. The goal of this review is to provide an overview of AS, from the pathophysiological changes that occur as the disease progresses, to genetic factors that are involved with its onset. Considering the high prevalence in the population, and the debilitating life changes that occur as a result of the disease, a strong emphasis is placed on the diagnostic imaging methods that are used to detect this condition, as well as several treatment methods that could improve the health of individuals diagnosed with AS. PMID:26435775

What Predicts Children's Fixed and Growth Intelligence Mind-Sets? Not Their Parents' Views of Intelligence but Their Parents' Views of Failure.

PubMed

Haimovitz, Kyla; Dweck, Carol S

2016-06-01

Children's intelligence mind-sets (i.e., their beliefs about whether intelligence is fixed or malleable) robustly influence their motivation and learning. Yet, surprisingly, research has not linked parents' intelligence mind-sets to their children's. We tested the hypothesis that a different belief of parents-their failure mind-sets-may be more visible to children and therefore more prominent in shaping their beliefs. In Study 1, we found that parents can view failure as debilitating or enhancing, and that these failure mind-sets predict parenting practices and, in turn, children's intelligence mind-sets. Study 2 probed more deeply into how parents display failure mind-sets. In Study 3a, we found that children can indeed accurately perceive their parents' failure mind-sets but not their parents' intelligence mind-sets. Study 3b showed that children's perceptions of their parents' failure mind-sets also predicted their own intelligence mind-sets. Finally, Study 4 showed a causal effect of parents' failure mind-sets on their responses to their children's hypothetical failure. Overall, parents who see failure as debilitating focus on their children's performance and ability rather than on their children's learning, and their children, in turn, tend to believe that intelligence is fixed rather than malleable. © The Author(s) 2016.

Phenotypic Correction of Hemophilia A in Sheep by Postnatal Intraperitoneal Transplantation of FVIII-Expressing MSC

PubMed Central

Porada, Christopher D.; Sanada, Chad; Kuo, Chung-Jung; Colletti, Evan; Mandeville, Walter; Hasenau, John; Zanjani, Esmail D.; Moot, Robert; Doering, Christopher; Spencer, H. Trent; Almeida-Porada, Graça

2011-01-01

We recently re-established a line of sheep that accurately mimics the clinical symptoms and genetics of severe hemophilia A (HA). Herein, we tested a novel, non-ablative transplant therapy in 2 pediatric HA animals. Paternal mesenchymal stem cells (MSC) were transduced with a porcine FVIII-encoding lentivector, and transplanted via the intraperitoneal route, without preconditioning. At the time of transplantation, these animals had received multiple hFVIII treatments for various spontaneous bleeds, and had developed debilitating hemarthroses which produced severe defects in posture and gait. Transplantation of transduced MSC resolved all existent hemarthroses, and spontaneous bleeds ceased. Damaged joints recovered fully; the animals regained normal posture and gait and resumed normal activity. Despite achieving factor-independence, a sharp rise in pre-existent Bethesda titers occurred following transplantation, decreasing the effectiveness and duration of therapy. Post-mortem examination revealed widespread engraftment, with MSC present within the lung, liver, intestine, and thymus, but particularly within joints affected at the time of transplantation, suggesting MSC homed to sites of ongoing injury/inflammation to release FVIII, explaining the dramatic improvement in hemarthrotic joints. In summary, this novel, non-ablative MSC transplantation was straightforward, safe, and converted life-threatening, debilitating HA to a moderate phenotype in a large animal model. PMID:21906573

Docetaxel-related fatigue in men with metastatic prostate cancer: a descriptive analysis.

PubMed

Bergin, A R T; Hovey, E; Lloyd, A; Marx, G; Parente, P; Rapke, T; de Souza, P

2017-09-01

Fatigue is a prevalent and debilitating side effect of docetaxel chemotherapy in metastatic prostate cancer. A better understanding of the kinetics and nature of docetaxel-related fatigue may provide a framework for intervention. This secondary analysis was performed using the MOTIF database, from a phase III, randomised, double-blind, placebo-controlled study of modafinil (200 mg/day for 15 days) for docetaxel-related fatigue in men with metastatic prostate cancer [1]. The pattern of fatigue was analysed using the MDASI (MD Anderson Symptom Inventory) score. The impact of modafinil, cumulative docetaxel exposure, age and smoking status on fatigue kinetics were explored. Fatigue-related symptoms were assessed using the SOMA6 (fatigue and related symptoms) subset of the SPHERE (Somatic and Psychological Health Report). Mood was tracked using the short form 36 health survey questionnaire (SF-36). Across four docetaxel cycles, fatigue scores were higher in the first week and decreased over weeks two and three. Whilst men randomised to modafinil had reduced fatigue scores, cumulative docetaxel had little impact. Younger men (55-68 years) had significantly reduced fatigue scores, whereas current and ex-smokers had higher scores. There was no significant change in mood status or haemoglobin across treatment cycles. Men described both 'somnolence' and 'muscle fatigue' contributing significantly to their symptom complex. Assessment and management of docetaxel-related fatigue remains an important challenge. Given the complex, multifactorial nature of fatigue, identification through structured interview and interventions targeted to specific 'at risk' groups may be the most beneficial. Understanding the temporal pattern (kinetics) and nature of fatigue is critical to guide this process.

Exploratory Investigation of Early Biomarkers for Chronic Fatigue in Prostate Cancer Patients Following Radiation Therapy

PubMed Central

Feng, Li Rebekah; Wolff, Brian S.; Lukkahatai, Nada; Espina, Alexandra; Saligan, Leorey N.

2016-01-01

Background Fatigue is one of the most debilitating side effects of cancer therapy. Identifying biomarkers early during cancer therapy may help us understand the biologic underpinnings of the persistence of fatigue following therapy. Objective We aimed to identify early biomarkers of fatigue by examining correlations of levels of cytokines during external beam radiation therapy (EBRT) with persistence of fatigue one year following treatment completion in men with non-metastatic prostate cancer (NM-PC). Methods A sample of 34 men with NM-PC scheduled to receive EBRT were followed at baseline (T1), midpoint of EBRT (T2), and one year following EBRT (T3). Demographic and clinical data were obtained by chart review. The Functional Assessment of Cancer Therapy-Fatigue (FACT-F) was administered to measure fatigue levels. Plasma cytokine levels were determined at T1 and T2 using the Bio-Rad Bio-Plex Cytokine Assay Kits. Results Significant correlations were observed between levels of IL-3, IL-8, IL-9, IL-10, IL-16, IP10, IFNα2, IFNγ, and SDF1α at T2 with worsening of fatigue from T1 to T3. Conclusions Immunological changes prior to chronic fatigue development may reflect the long term response to radiation therapy-induced damage. Implications for Practice Early biomarkers for chronic fatigue related to cancer therapy will help advance our understanding of the etiology of this distressing symptom and will help nurses identify patients at risk for developing chronic fatigue after cancer treatment. This information will also aide in patient education, as well as symptom management. PMID:27105468

Successful treatment of asymptomatic or clinically terminal bovine Mycobacterium avium subspecies paratuberculosis infection (Johne disease) with the bacterium Dietzia used as a probiotic alone or in combination with dexamethasone

PubMed Central

2011-01-01

A naturally occurring gastrointestinal disease, primarily of ruminants (Johne disease), is a chronic debilitating disease that is caused by Mycobacterium avium subspecies paratuberculosis (MAP). MAP infection occurs primarily in utero and in newborns. Outside our Dietzia probiotic treatment, there are no preventive/curative therapies for bovine paratuberculosis. Interestingly, MAP is at the center of controversy as to its role in (cause of) Crohn disease (CD) and more recently, its role in diabetes, ulcerative colitis, and irritable bowel syndrome (IBS); the latter two, like CD, are considered to be a result of chronic intestinal inflammation. Treatments, both conventional and biologic agents, which induce and maintain remission are directed at curtailing processes that are an intricate part of inflammation. Most possess side effects of varying severity, lose therapeutic value, and more importantly, none routinely result in prevention and/or cures. Based on (a) similarities of Johne disease and Crohn disease, (b) a report that Dietzia inhibited growth of MAP under specific culture conditions, and (c) findings that Dietzia when used as a probiotic, (i) was therapeutic for adult bovine paratuberculosis, and (ii) prevented development of disease in MAP-infected calves, the goal of the present investigations was to design protocols that have applicability for IBD patients. Dietzia was found safe for cattle of all ages and for normal and immunodeficient mice. The results strongly warrant clinical evaluation as a probiotic, in combination with/without dexamethasone. PMID:21460639

Successful treatment of asymptomatic or clinically terminal bovine Mycobacterium avium subspecies paratuberculosis infection (Johne's disease) with the bacterium Dietzia used as a probiotic alone or in combination with dexamethasone: Adaption to chronic human diarrheal diseases.

PubMed

Click, Robert E

2011-01-01

A naturally occurring gastrointestinal disease, primarily of ruminants (Johne disease), is a chronic debilitating disease that is caused by Mycobacterium avium subspecies paratuberculosis (MAP). MAP infection occurs primarily in utero and in newborns. Outside our Dietzia probiotic treatment, there are no preventive/curative therapies for bovine paratuberculosis. Interestingly, MAP is at the center of controversy as to its role in (cause of) Crohn disease (CD) and more recently, its role in diabetes, ulcerative colitis, and irritable bowel syndrome (IBS); the latter two, like CD, are considered to be a result of chronic intestinal inflammation. Treatments, both conventional and biologic agents, which induce and maintain remission are directed at curtailing processes that are an intricate part of inflammation. Most possess side effects of varying severity, lose therapeutic value, and more importantly, none routinely result in prevention and/or cures. Based on (a) similarities of Johne disease and Crohn disease, (b) a report that Dietzia inhibited growth of MAP under specific culture conditions, and (c) findings that Dietzia when used as a probiotic, (i) was therapeutic for adult bovine paratuberculosis, and (ii) prevented development of disease in MAP-infected calves, the goal of the present investigations was to design protocols that have applicability for IBD patients. Dietzia was found safe for cattle of all ages and for normal and immunodeficient mice. The results strongly warrant clinical evaluation as a probiotic, in combination with/without dexamethasone.

Mechanisms of Aquaporin-Facilitated Cancer Invasion and Metastasis

NASA Astrophysics Data System (ADS)

De Ieso, Michael L.; Yool, Andrea J.

2018-04-01

Cancer is a leading cause of death worldwide, and its incidence is rising with numbers expected to increase 70% in the next two decades. The fact that current mainline treatments for cancer patients are accompanied by debilitating side effects prompts a growing demand for new therapies that not only inhibit growth and proliferation of cancer cells, but also control invasion and metastasis. One class of targets gaining international attention is the aquaporins, a family of membrane-spanning water channels with diverse physiological functions and extensive tissue-specific distributions in humans. Aquaporins -1, -2, -3, -4, -5, -8, and -9 have been linked to roles in cancer proliferation, invasion and metastasis, but their mechanisms of action remain to be fully defined. Aquaporins are implicated in the metastatic cascade in processes of angiogenesis, cellular dissociation, migration and invasion. Cancer invasion and metastasis are proposed to be potentiated by aquaporins in boosting tumor angiogenesis, enhancing cell volume regulation, regulating cell-cell and cell-matrix adhesions, interacting with actin cytoskeleton, regulating proteases and extracellular-matrix degrading molecules, contributing to the regulation of epithelial-mesenchymal transitions, and interacting with signaling pathways enabling motility and invasion. Pharmacological modulators of aquaporin channels are being identified and tested for therapeutic potential, including compounds derived from loop diuretics, metal-containing organic compounds, plant natural products, and other small molecules. Further studies on aquaporin-dependent functions in cancer metastasis are needed to define the differential contributions of different classes of aquaporin channels to regulation of fluid balance, cell volume, small solute transport, signal transduction, their possible relevance as rate limiting steps, and potential values as therapeutic targets for proliferation and invasion.

Fatigue in Adolescents With Cancer Compared to Healthy Adolescents

PubMed Central

Daniel, Lauren C.; Brumley, Lauren D.; Schwartz, Lisa A.

2015-01-01

Background Cancer-related fatigue is one of the most pervasive and debilitating side-effects of cancer treatment and adolescents consistently rate cancer-related fatigue as one of the most distressing aspects of treatment. Because fatigue is also high in adolescents without cancer, the current study aims to describe fatigue in adolescents with cancer relative to a control group and to identify associates of such fatigue. Knowing this is important for understanding the extent of the problem in adolescents with cancer relative to healthy adolescents and for understanding who is most at risk for fatigue and related distress. Procedure Adolescents with cancer and their caregivers (n =102) and adolescents without a history of chronic health conditions and their caregivers (n =97) completed the Multidimensional Fatigue Scale and measures of depression, quality of life (QoL), affect, coping, and family functioning. Results Adolescents with cancer and their caregivers reported significantly more adolescent fatigue across all domains (with the exception of adolescent reports of cognitive fatigue) relative to adolescents without chronic health conditions. Higher fatigue was significantly related to adolescent report of more symptoms of depression, poorer QoL, higher negative affect, less positive affect, and behavioral disengagement coping style. Fatigue was not related to active coping or family functioning. Conclusions Adolescents with cancer experience significantly more fatigue than peers without chronic health conditions. Reports of fatigue are closely related to multiple indicators of psychosocial well-being, suggesting that fatigue may be an important cancer-related symptom to assess and manage to improve adolescent QoL. PMID:23897651

Footwear width and balance-recovery reactions: A new approach to improving lateral stability in older adults.

PubMed

Yamaguchi, Takeshi; Cheng, Kenneth C; McKay, Sandra M; Maki, Brian E

Age-related difficulty in controlling lateral stability is of crucial importance because lateral falls increase risk of debilitating hip-fracture injury. This study examined whether a small increase in footwear sole width can improve ability of older adults to regain lateral stability subsequent to balance perturbation. The study involved sixteen healthy, ambulatory, community-dwelling older adults (aged 65-78). Widened base-of-support (WBOS) footwear was simulated by affixing polystyrene-foam blocks (20mm wide) on the medial and lateral sides of rubber overshoes; unaltered overshoes were worn in normal (NBOS) trials. Balance perturbations were applied using a motion platform. Gait, mobility and agility tests revealed no adverse effects of wearing the WBOS footwear. Lateral-perturbation tests showed that the WBOS footwear improved ability to stabilize the body without stepping (p=0.002). Depending on the perturbation magnitude, the frequency of stepping was reduced by up to 25% (64% of NBOS trials vs 39% of WBOS trials). In addition, the WBOS footwear appeared to improve ability to maintain lateral stability during forward-step reactions, as evidenced by reduced incidence of additional lateral steps (p=0.04) after stepping over an obstacle in response to a forward-fall perturbation. A small increase in sole width can improve certain aspects of lateral stability in older adults, without compromising mobility and agility. This finding supports the viability of WBOS footwear as an intervention to improve balance. Further research is needed to test populations with more severe balance impairments, examine user compliance, and determine if WBOS footwear actually reduces falling risk in daily life.

Migraine headache and labor market outcomes.

PubMed

Rees, Daniel I; Sabia, Joseph J

2015-06-01

While migraine headache can be physically debilitating, no study has attempted to estimate its effects on labor market outcomes. Using data drawn from the National Longitudinal Study of Adolescent Health, we estimate the effect of being diagnosed with migraine headache on labor force participation, hours worked, and wages. Ordinary least squares (OLS) estimates suggest that migraines are associated with reduced labor force participation and lower wages among females. A negative association between migraine headache and the wages of female respondents is also obtained using an instrumental variables (IV) approach, although the IV estimates are imprecise relative to the OLS estimates. Copyright © 2014 John Wiley & Sons, Ltd.

The Peacock versus the louse (pediculus humanus corporis): one soldier's contribution to combating trench fever in the First World War.

PubMed

Peacock, A; Pearson, W

2010-09-01

Trench fever became a major worry for the Allied High Command during the First World War because of its debilitating effects on troop performance. The causes of the fever were not previously known, but entomological research identified the body louse (pediculus humanus corporis) as the carrier, and the Royal Army Medical Corps developed effective methods of control through disinfestation. These were markedly influenced by the researches of a young entomologist, Alexander David Peacock, which were conducted under campaign conditions. Peacock subsequently occupied a Chair of Zoology at St. Andrews University for 30 years.

Complex Regional Pain Syndrome Type I Affects Brain Structure in Prefrontal and Motor Cortex

PubMed Central

Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

2014-01-01

The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the “non-flipped” data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the “flipped” data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control. PMID:24416397

A systematic review of variations of the recurrent laryngeal nerve.

PubMed

Ling, Xing Yao; Smoll, Nicolas Roydon

2016-01-01

With thyroid cancer fast becoming one of the most common endocrine cancers, the frequency of thyroid surgery has increased. A common and debilitating concern with thyroid surgery is recurrent laryngeal nerve (RLN) paralysis leading to glottal obstruction and airway compromise. A systematic review regarding the anatomical variation of the recurrent laryngeal nerve was performed to determine the position of anatomical variants of the RLN in relation to the inferior thyroid artery (ITA) as well as the prevalence of nonrecurrent laryngeal nerve (NRLN). MEDLINE, Web of Science, MEDITEXT, AMED, CINAHL, Cochrane, ProQuest, Pubmed, and ScienceDirect. Databases were searched using the search terms "inferior thyroid artery," "recurrent laryngeal nerve," "nonrecurrent laryngeal nerve," and "anatomical variation." The reference sections of the articles found were searched for additional reports. The references of all articles were searched to find articles missed in the database search. A total of 8,655 RLN sides were included in this study. One thousand eight hundred and thirteen (20.95%; 95% confidence interval (CI) 20.09, 2,182) showed a Type A configuration of RLN in relation to the ITA, 2,432 (28.10%; 95% CI 27.15, 29.06) showed a Type B configuration and 4,410 (50.95%; 95% CI 49.89, 52.01) showed a Type C configuration between the RLN and the ITA. The second search returned with 38,568 recurrent laryngeal sides and only 221 (0.57%; 95%CI 0.5, 0.65) NRLN documented. The RLN is most commonly found in the posterior position, relative to the ITA. The incidence of the NRLN is low, only occurring in 0.57% of people. © 2015 Wiley Periodicals, Inc.

Skull Flexure from Blast Waves: A Mechanism for Brain Injury with Implications for Helmet Design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moss, W C; King, M J; Blackman, E G

2009-04-30

Traumatic brain injury [TBI] has become a signature injury of current military conflicts, with debilitating, costly, and long-lasting effects. Although mechanisms by which head impacts cause TBI have been well-researched, the mechanisms by which blasts cause TBI are not understood. From numerical hydrodynamic simulations, we have discovered that non-lethal blasts can induce sufficient skull flexure to generate potentially damaging loads in the brain, even without a head impact. The possibility that this mechanism may contribute to TBI has implications for injury diagnosis and armor design.

Etiology, evaluation, and management of xerostomia.

PubMed

Millsop, Jillian W; Wang, Elizabeth A; Fazel, Nasim

Xerostomia is defined as the complaint of oral dryness. It is a condition that primarily affects older adults and can have a significant negative effect on one's quality of life. Patients with xerostomia often do not have objective signs of hyposalivation. The underlying etiology of xerostomia includes a variety of systemic diseases and local factors. Our aim is to provide a comprehensive review of the differential diagnosis, evaluation, and management of xerostomia. Prompt diagnosis and management can alleviate the clinical manifestations of this debilitating condition. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic and environmental origins of health anxiety: a twin study

PubMed Central

TAYLOR, STEVEN; THORDARSON, DANA S; JANG, KERRY L; ASMUNDSON, GORDON J.G

2006-01-01

Excessive health anxiety - which is anxiety about one's health that is disproportionate to the person's medical status - is a common and often debilitating problem. Little is known about its etiology. The present study investigated the role of genetic and environmental factors using a classic twin study method. Results indicated that, after controlling for medical morbidity, environmental influences accounted for most of individual differences in health anxiety. These findings underscore the importance of psychosocial interventions, which have been shown to be among the most effective interventions for excessive health anxiety. PMID:16757996

A unified frame of predicting side effects of drugs by using linear neighborhood similarity.

PubMed

Zhang, Wen; Yue, Xiang; Liu, Feng; Chen, Yanlin; Tu, Shikui; Zhang, Xining

2017-12-14

Drug side effects are one of main concerns in the drug discovery, which gains wide attentions. Investigating drug side effects is of great importance, and the computational prediction can help to guide wet experiments. As far as we known, a great number of computational methods have been proposed for the side effect predictions. The assumption that similar drugs may induce same side effects is usually employed for modeling, and how to calculate the drug-drug similarity is critical in the side effect predictions. In this paper, we present a novel measure of drug-drug similarity named "linear neighborhood similarity", which is calculated in a drug feature space by exploring linear neighborhood relationship. Then, we transfer the similarity from the feature space into the side effect space, and predict drug side effects by propagating known side effect information through a similarity-based graph. Under a unified frame based on the linear neighborhood similarity, we propose method "LNSM" and its extension "LNSM-SMI" to predict side effects of new drugs, and propose the method "LNSM-MSE" to predict unobserved side effect of approved drugs. We evaluate the performances of LNSM and LNSM-SMI in predicting side effects of new drugs, and evaluate the performances of LNSM-MSE in predicting missing side effects of approved drugs. The results demonstrate that the linear neighborhood similarity can improve the performances of side effect prediction, and the linear neighborhood similarity-based methods can outperform existing side effect prediction methods. More importantly, the proposed methods can predict side effects of new drugs as well as unobserved side effects of approved drugs under a unified frame.

Drug side effect extraction from clinical narratives of psychiatry and psychology patients

PubMed Central

Kocher, Jean-Pierre A; Chute, Christopher G; Savova, Guergana K

2011-01-01

Objective To extract physician-asserted drug side effects from electronic medical record clinical narratives. Materials and methods Pattern matching rules were manually developed through examining keywords and expression patterns of side effects to discover an individual side effect and causative drug relationship. A combination of machine learning (C4.5) using side effect keyword features and pattern matching rules was used to extract sentences that contain side effect and causative drug pairs, enabling the system to discover most side effect occurrences. Our system was implemented as a module within the clinical Text Analysis and Knowledge Extraction System. Results The system was tested in the domain of psychiatry and psychology. The rule-based system extracting side effects and causative drugs produced an F score of 0.80 (0.55 excluding allergy section). The hybrid system identifying side effect sentences had an F score of 0.75 (0.56 excluding allergy section) but covered more side effect and causative drug pairs than individual side effect extraction. Discussion The rule-based system was able to identify most side effects expressed by clear indication words. More sophisticated semantic processing is required to handle complex side effect descriptions in the narrative. We demonstrated that our system can be trained to identify sentences with complex side effect descriptions that can be submitted to a human expert for further abstraction. Conclusion Our system was able to extract most physician-asserted drug side effects. It can be used in either an automated mode for side effect extraction or semi-automated mode to identify side effect sentences that can significantly simplify abstraction by a human expert. PMID:21946242

What matters when judging intentionality-moral content or normative status? Testing the rational scientist model of the side-effect.

PubMed

Papadopoulos, C; Hayes, B K

2018-06-01

Previous work has demonstrated a "side-effect effect," such that intentionality is more likely to be attributed to agents who bring about negatively valenced as opposed to positively valenced side effects. The rational-scientist model explains this by suggesting that norm-violating side effects are more informative for inferring intentionality than norm-conforming side effects. In the present study we reexamined this account, addressing limitations of previous empirical tests (e.g., Uttich & Lombrozo, Cognition 116: 87-100, 2010). Side-effect valence and norm status were manipulated factorially, enabling an examination of the impact of norm status on intentionality judgments in both positively and negatively valenced side effects. Additionally, the impact of side-effect norm status on the perceived valences of side effects and agents was examined. Effects of norm status were found for both positive and negative side effects. Violation of an ostensibly neutral norm led to negative perceptions of the side effect. However, a norm status effect on intentionality judgments persisted when these effects were controlled. These results support the view that the side-effect effect is the result of the rational use of social-cognitive evidence.

Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study

PubMed Central

Haas, Marion; Viney, Rosalie; Pearson, Sallie-Anne; Haywood, Philip; Brown, Chris; Ward, Robyn

2017-01-01

Aim Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. Methods We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Results Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. Conclusion This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers. PMID:29016607

Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study.

PubMed

Pearce, Alison; Haas, Marion; Viney, Rosalie; Pearson, Sallie-Anne; Haywood, Philip; Brown, Chris; Ward, Robyn

2017-01-01

Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers.

Side effects associated with anti-HIV drugs.

PubMed

Highleyman, L

1998-04-01

Many side effects are associated with the use of anti-HIV drugs, impacting the development of drug resistance and the quality of life for HIV-patients. Concern about side effects is a primary factor in deterring people from beginning HIV therapy. Frequency and severity of side effects vary greatly, but they are frequently more common and severe in people who are taking a new drug or who have advanced HIV disease. Information on side effects comes largely from clinical trials; however, many side effects are not discovered until the drug has been approved and used by larger numbers of people. Side effects vary from serious toxicities that require stopping treatment to uncomfortable or annoying side effects that interfere with daily life. A table categorizes the four major side effects (nausea, fever, skin rash, and fatigue) and divides them into grades that describe their intensity. A chart lists the side effects associated with specific anti-HIV drugs. Suggestions for managing side effects are included.

The Chicken or the Egg? The Direction of the Relationship Between Mathematics Anxiety and Mathematics Performance

PubMed Central

Carey, Emma; Hill, Francesca; Devine, Amy; Szücs, Dénes

2016-01-01

This review considers the two possible causal directions between mathematics anxiety (MA) and poor mathematics performance. Either poor maths performance may elicit MA (referred to as the Deficit Theory), or MA may reduce future maths performance (referred to as the Debilitating Anxiety Model). The evidence is in conflict: the Deficit Theory is supported by longitudinal studies and studies of children with mathematical learning disabilities, but the Debilitating Anxiety Model is supported by research which manipulates anxiety levels and observes a change in mathematics performance. It is suggested that this mixture of evidence might indicate a bidirectional relationship between MA and mathematics performance (the Reciprocal Theory), in which MA and mathematics performance can influence one another in a vicious cycle. PMID:26779093

Side Effect Perceptions and Their Impact on Treatment Decisions in Women.

PubMed

Waters, Erika A; Pachur, Thorsten; Colditz, Graham A

2017-04-01

Side effects prompt some patients to forego otherwise-beneficial therapies. This study explored which characteristics make side effects particularly aversive. We used a psychometric approach, originating from research on risk perception, to identify the factors (or components) underlying side effect perceptions. Women ( N = 149) aged 40 to 74 years were recruited from a patient registry to complete an online experiment. Participants were presented with hypothetical scenarios in which an effective and necessary medication conferred a small risk of a single side effect (e.g., nausea, dizziness). They rated a broad range of side effects on several characteristics (e.g., embarrassing, treatable). In addition, we collected 4 measures of aversiveness for each side effect: choosing to take the medication, willingness to pay to avoid the side effect (WTP), negative affective attitude associated with the side effect, and how each side effect ranks among others in terms of undesirability. A principal components analysis (PCA) was used to identify the components underlying side effect perceptions. Then, for each aversiveness measure separately, regression analyses were used to determine which components predicted differences in aversiveness among the side effects. The PCA revealed 4 components underlying side effect perceptions: affective challenge (e.g., frightening), social challenge (e.g., disfiguring), physical challenge (e.g., painful), and familiarity (e.g., common). Side effects perceived as affectively and physically challenging elicited the highest levels of aversiveness across all 4 measures. Understanding what side effect characteristics are most aversive may inform interventions to improve medical decisions and facilitate the translation of novel biomedical therapies into clinical practice.

Side Effect Perceptions and their Impact on Treatment Decisions in Women

PubMed Central

Waters, Erika A.; Pachur, Thorsten; Colditz, Graham A.

2016-01-01

Background Side effects prompt some patients to forego otherwise-beneficial therapies. This study explored which characteristics make side effects particularly aversive. Methods We used a psychometric approach, originating from research on risk perception, to identify the factors (or components) underlying side effect perceptions. Women (N=149) aged 40–74 were recruited from a patient registry to complete an online experiment. Participants were presented with hypothetical scenarios in which an effective and necessary medication conferred a small risk of a single side effect (e.g., nausea, dizziness). They rated a broad range of side effects on several characteristics (e.g., embarrassing, treatable). In addition, we collected four measures of aversiveness for each side effect: choosing to take the medication, willingness to pay to avoid the side effect (WTP), negative affective attitude associated with the side effect, and how each side effect ranks among others in terms of undesirability. A principle-components analysis (PCA) was used to identify the components underlying side effect perceptions. Then, for each aversiveness measure separately, regression analyses were used to determine which components predicted differences in aversiveness among the side effects. Results The PCA revealed four components underlying side effect perceptions: affective challenge (e.g., frightening), social challenge (e.g., disfiguring), physical challenge (e.g., painful), and familiarity (e.g., common). Side effects perceived as affectively and physically challenging elicited the highest levels of aversiveness across all four measures. Conclusions Understanding what side effect characteristics are most aversive may inform interventions to improve medical decisions and facilitate the translation of novel biomedical therapies into clinical practice. PMID:27216581

Effect of Communication Style on Perceptions of Medication Side Effect Risk among Pharmacy Students.

PubMed

Sawant, Ruta V; Beatty, Collin R; Sansgiry, Sujit S

2016-10-25

Objective. To assess the effect of communication style, and frequency and severity of medication side-effects, on pharmacy students' perception of risk of experiencing side effects. Methods. One hundred responses from pharmacy students were obtained using an online survey. Participants were presented with a drug information box containing drug name, drug usage, and one side-effect associated with the drug. Information on side-effect for each drug was presented in one of eight experimental conditions, in a 2 (side-effect frequency: low, high), X2 (side-effect severity: mild, severe) X2 (communication style: verbal, verbal + natural frequency) factorial design. Risk perception of experiencing side effects was measured. Results. Communication style was found to have a significant impact on risk perception depending on the context of frequency and severity associated with the side effect. Conclusion. Communication style plays a significant role in formulating risk perceptions of medication side effects. Training in pharmaceutical counseling should include special emphasis on effective language use.

Hyperemesis Gravidarum (HG)

MedlinePlus

... of vomiting (e.g. gastric ulcers, esophageal bleeding, malnutrition, etc.) may also contribute to and worsen ongoing ... vomiting include debilitating fatigue, gastric irritation, ketosis, and malnutrition. Aggressive care early in pregnancy is very important ...

Shortness of Breath

MedlinePlus

... with blood clots in the legs or pelvis (deep venous thrombosis), debilitating medical conditions, immobility, or inherited ... it hard for a person to take a deep breath, which usually results in retention of carbon ...

Arthroscopic capsular plication for microtraumatic anterior shoulder instability in overhead athletes.

PubMed

Jones, Kristofer J; Kahlenberg, Cynthia A; Dodson, Christopher C; Nam, Denis; Williams, Riley J; Altchek, David W

2012-09-01

Extreme loading conditions at the glenohumeral joint during overhead athletic activities can result in both soft tissue and osseous adaptative changes at the shoulder. Subtle alterations in the stabilizing structures may lead to anterior instability and debilitating shoulder pain with subsequent inability to participate in athletics. There is currently a paucity of data documenting clinical outcomes after arthroscopic capsular plication in overhead athletes who demonstrate objective findings of pain and anterior instability on physical examination. To evaluate outcomes after arthroscopic capsular plication for anterior instability in overhead athletes with an emphasis on postoperative range of motion, postoperative shoulder function, and return to sport. Case series; Level of evidence, 4. The authors identified 20 overhead athletes with debilitating shoulder pain and a failed trial of nonoperative management who underwent arthroscopic capsular plication (12 suture plication, 8 suture anchor plication) for anterior instability related to isolated capsular redundancy. Patients were evaluated with the Single Assessment Numerical Evaluation (SANE) and Kerlan-Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow Score, and they were interviewed to determine the rate of return to athletic activity. Failures of treatment included patients who demonstrated debilitating pain that precluded return to sport. At a mean follow-up of 3.6 years (range, 2.0-5.5 years), 18 (90%) patients returned to overhead sports, with 17 (85%) at their preinjury level. The mean (SD) SANE score was 86 (17.5%; range, 30%-100%), and the mean (SD) KJOC score was 82 (18.2; range, 28-100). When compared with the contralateral extremity, there were no significant differences in glenohumeral range of motion. Two patients with associated rotator cuff injury experienced persistent pain with overhead activity and were unable to return to sport, representing a 10% failure rate. Arthroscopic capsular plication for anterior instability related to isolated capsular redundancy is an effective procedure that yields a high rate of patient satisfaction and return to overhead athletic activity with an acceptably low failure rate. Patients with associated rotator cuff injury may be at higher risk for treatment failure.

Health Related Quality of Life in Patients with Side-Effects after Antimuscarinic Treatment for Overactive Bladder.

PubMed

Kim, Aram; Lee, Kyu-Sung; Jung, Rangrhee; Na, Selee; Kim, Joon-Chul; Kim, Hyeong Gon; Choo, Myung-Soo

2017-09-01

Drug therapy is the mainstay of treatment for overactive bladder (OAB), but antimuscarinic agents possess side-effects. These side-effects decrease the patients' quality of life. We therefore assessed the impact of side-effects on health-related quality of life (HR-QoL) through an analysis of EQ-5D questionnaire. This study was designed to investigate the patients' satisfaction by quality weight of health status as affected by the side-effects of OAB medications. Patients who had OAB symptoms lasting longer than 3 months and have experienced side-effects after any antimuscarinic treatments filled in the EQ-5D questionnaire. The enrolled patients had two EQ-5D questionnaires for two different health statuses, i.e., presence or absence of side-effects. Quality weight was calculated using the ED-5D health status score with Korean tariff. One hundred patients were enrolled and completed the HR-QoL questionnaire. The most prevalent side-effect was dry mouth (61%) and 28% patients had dry mouth and constipation concurrently. Most of the patients with side-effects tried to endure and overcome these side-effects (79%), but 10% desired a change in medication, and 6% stopped medication altogether. The quality weight of EQ-5D without side-effects was 0.863, while the quality weight with side-effects was 0.666 (P < 0.001). The VAS score was 79 in patient without side-effects and 57 in those with side-effects, supporting the results of quality weight assessment. Overactive bladder patients may enjoy a better quality of life if side-effects associated with antimuscarinic therapy are fewer. © 2016 John Wiley & Sons Australia, Ltd.

Current protocols in the management of oral submucous fibrosis: An update.

PubMed

Arakeri, Gururaj; Rai, Kirthi Kumar; Boraks, George; Patil, Shekar Gowda; Aljabab, Abdulsalam S; Merkx, M A W; Carrozzo, Marco; Brennan, Peter A

2017-07-01

Oral submucous fibrosis (OSMF) is a debilitating condition of oral cavity which has significant potential for malignant transformation. In spite of over 20 years of research, the pathogenesis of the condition is still obscure and no single management modality is effective. Many OSMF treatment protocols have been proposed to alleviate the signs and symptoms of the disorder and there is overwhelming evidence that as areca nut is primary cause, stopping its use may have a considerable effect on symptoms rather than reversing pre-existing fibrosis. We present a review of the current protocols for managing OSMF. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Achievement Motivation and Fear of Failure in Family and School

ERIC Educational Resources Information Center

Hermans, Hubert J. M.; And Others

1972-01-01

Results indicate that the achievement motivation and the debilitating anxiety of the child manifest themselves in the social interaction patterns both within the family and within the classroom. (Authors)

Explanations for side effect aversion in preventive medical treatment decisions

PubMed Central

Waters, Erika A.; Weinstein, Neil D.; Colditz, Graham A.; Emmons, Karen

2008-01-01

Objective Many laypeople demonstrate excessive sensitivity to negative side effects of medical treatments, which may lead them to refuse beneficial therapies. This Internet-based experiment investigated three possible explanations for such “side effect aversion.” One was derived from mental accounting, one examined the mere presence of a side effect, and one focused on computational difficulties. Design Participants (N = 5,379) were presented with a hypothetical cancer preventive treatment situation that was or was not accompanied by one or two small side effects. The side effects were either beneficial or harmful. In all conditions the net absolute risk reduction associated with the treatment was 15%. Main Outcome Measures Participants indicated their willingness to accept treatment and their perceptions of the treatment’s effects on their overall cancer risk. Results Data were consistent only with the “mere presence” explanation of side effect aversion, the idea that side effects act as a strong negative cue that directly affects treatment appraisal. The number of negative side effects did not influence treatment willingness. Conclusion Side effect aversion is a challenge to informed decision making. Specific mechanisms that produce side effect aversion should be identified. PMID:19290712

Subjective Report of Side Effects of Prescribed and Nonprescribed Psychostimulant Use in Young Adults.

PubMed

Smith, Tess E; Martel, Michelle M; DeSantis, Alan D

2017-03-21

Side effects of prescribed and nonprescribed psychostimulant use are understudied. The study examined side effects of prescribed and nonprescribed psychostimulant use in a college sample with attention to possible gender differences. 2716 undergraduates (1448 male) between the ages of 17 and 57 years (M = 19.43 years, SD = 1.7 years) completed an online survey that included questions about the subjective side effects of prescribed and nonprescribed psychostimulant use. Results suggested that prescribed users more frequently reported side effects, compared to nonprescribed users. For prescribed users, females more frequently reported appetite, somatic, and anxiety-related side effects compared to males. For nonprescribed users, while females reported more somatic and anxiety-related side effects, males more frequently reported loss of sex drive and sweating as side effects. Conclusions/Importance: These findings suggest prescribed users of psychostimulants more frequently report side effects with prominent gender differences in line with gender roles.

Sexual side effects associated with conventional and atypical antipsychotics.

PubMed

Compton, M T; Miller, A H

2001-01-01

The sexual side effects of psychotropic medications are becoming increasingly recognized in clinical psychiatry. The magnitude of the problem of sexual side effects associated with antipsychotic medications has yet to be fully elucidated, but a multitude of references in the literature demonstrate the importance of these side effects in both men and women. All currently used antipsychotic medications are associated with sexual side effects of various types. Although each antipsychotic medication may have a specific side effect profile determined by its various receptor affinities and by the degree to which it elevates serum prolactin, there is currently no evidence that specific side effects can be predicted. Sexual side effects can be categorized according to the phase of the sexual response cycle with which they interfere. Suggestions for clinical evaluation and treatment options are provided, including risk factor modification, dose reduction, switching agents, and addition of other agents. Sexual side effects associated with conventional and atypical antipsychotic medications represent an underestimated and understudied set of side effects that may diminish a patient's quality of life and lead to treatment noncompliance. Clinicians prescribing antipsychotic medications should be familiar with the classification, evaluation, and treatment of these side effects.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Treatment

MedlinePlus

... practitioner, might help with pain for some patients. Depression, Stress, and Anxiety Adjusting to a chronic, debilitating ... Consequence Pathogens and Pathology (DHCPP) Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs ...

Arthritis of the hand - Rheumatoid

MedlinePlus

... Therapist? Media Find a Hand Surgeon Home Anatomy Rheumatoid Arthritis Email to a friend * required fields From * To * ... debilitating when it affects the hands and fingers. Rheumatoid arthritis is one of the most common forms of ...

Anti-Seizure Medications: Relief from Nerve Pain

MedlinePlus

... be debilitating and difficult to control. Nerve damage (neuropathy) can be caused by many conditions, including: Diabetes. ... and pain in your hands and feet (diabetic neuropathy). Shingles. Anyone who has had chickenpox is at ...

Alleviating debilitating, chronic constipation with colostomy after appendicostomy: a case study.

PubMed

Baig, Mirza K; Boyer, Mary Lou; Marquez, Helen; Wexner, Steven D

2005-12-01

Severe chronic constipation is a debilitating condition. Patients not only experience infrequent bowel movements, but also are often frustrated by the sensation of incomplete evacuation; pain; straining; daily use of enemas; and continual concerns regarding diet, fluids, and medications. Diagnostic tests are performed to rule out organic causes of the condition. Common treatment options consist of dietary fiber supplementation, dietary instruction, adequate fluid intake, enemas, and laxatives; additional noninvasive management includes biofeedback training and botulinum toxin type A injections. Surgery is rarely recommended, although a select group of patients may benefit from antegrade continence enema procedure. A female patient presented with a history of long-standing constipation. When antegrade continence enema offered no improvement and other treatment measures failed, she underwent successful laparoscopic-assisted sigmoid resection and end colostomy. This approach may provide options for patients in similar circumstances.

A possible case of complex regional pain syndrome of the nose?

PubMed

Faraj-Hakim, S; Bleys, R L A W; Buwalda, J; de Ru, J A

2012-01-01

We present a case report of a patient with a putative diagnosis of complex regional pain syndrome of the nose. We would like to bring this disorder to the attention of rhinologists. A 53-year-old man presented with a history of extreme, constant, debilitating pain in his nose that started after he underwent several extensive nasal surgeries. Examination revealed atrophic nasal mucous membranes at the nasal septum. No other abnormalities were found. The pain did not diminish despite administration of analgesics and neuropathic pain medications. We propose a diagnosis of complex regional pain syndrome of the nose. The large number of nasal surgeries performed worldwide and the far reaching consequences of this debilitating syndrome indicate that it merits further investigation to determine whether it is a distinct disorder that should be recognized as such.

Role of Catheter-directed Thrombolysis in Management of Iliofemoral Deep Venous Thrombosis.

PubMed

Chen, James X; Sudheendra, Deepak; Stavropoulos, S William; Nadolski, Gregory J

2016-01-01

The treatment for iliofemoral deep venous thrombosis (DVT) is challenging, as the use of anticoagulation alone can be insufficient for restoring venous patency and thus lead to prolongation of acute symptoms and an increased risk of chronic complications, including venous insufficiency and postthrombotic syndrome (PTS). In these cases, earlier and more complete thrombus removal can ameliorate acute symptoms and reduce long-term sequelae. Endovascular therapies involving the use of pharmacologic, mechanical, and combined pharmacomechanical modalities have been developed to achieve these goals. The most frequently used of these techniques, catheter-directed thrombolysis (CDT), involves the infusion of a thrombolytic agent through a multiple-side-hole catheter placed within the thrombosed vein to achieve high local doses and thereby break down the clot while minimizing systemic thrombolytic agent exposure. Randomized controlled trial results have indicated decreased PTS rates and improved venous patency rates in patients treated with CDT compared with these rates in patients treated with anticoagulation. The use of newer pharmacomechanical techniques, as compared with conventional CDT, reduces procedural times and thrombolytic agent doses and is the subject of ongoing investigations. Endovascular thrombus removal techniques offer a means to improve venous valvular function and decrease the risk of debilitating long-term complications such as PTS and are a promising option for treating patients with iliofemoral DVT. (©)RSNA, 2016.

Environment, physical activity, and neurogenesis: implications for prevention and treatment of Alzhemier's disease.

PubMed

Briones, Teresita L

2006-02-01

Age is the biggest risk factor for the development of neurodegenerative diseases. Consequently, as the population ages it becomes more critical to find ways to avoid the debilitating cost of neurodegenerative diseases such as Alzheimer's. Some of the non-invasive strategies that can potentially slow down the mental decline associated with aging are exercise and use of multi-sensory environmental stimulation. The beneficial effects of both exercise and multi-sensory environmental stimulation have been well-documented, thus it is possible that these strategies can either provide neuroprotection or increase resistance to the development of age-related cognitive problems.

Multiple sclerosis.

PubMed

Files, Daniel Kane; Jausurawong, Tani; Katrajian, Ruba; Danoff, Robert

2015-06-01

Multiple sclerosis (MS) is a chronic, debilitating disease that can have devastating effects. Presentation varies widely in symptoms, pace, and progression. In addition to a thorough history and physical examination, diagnostic tools required to diagnose MS and exclude other diagnoses include MRI, evoked potential testing, and cerebrospinal fluid analysis. Although the disease is not curable presently, quality of life can be improved by minimizing the frequency and severity of disease burden. Disease modification, symptom management, preservation of function, and treatment of psychosocial issues are paramount to enhance the quality of life for the patient affected with MS. Copyright © 2015 Elsevier Inc. All rights reserved.

Femorofemoral bypass grafting in high-risk patients.

PubMed

Deruyter, L; Caes, F; Van den Brande, P; Cham, B; Welch, W

1986-01-01

A total of 37 extra-anatomic femorofemoral bypasses were inserted for severe unilateral iliac artery stenosis or a thrombosed graft limb of an aorto-bifemoral bifurcation graft. All patients were severely debilitated and at high risk for direct aorto-iliac reconstruction. 30% suffered severe claudication; 70% had ischemic restpain or trophic lesions. 43% died during a mean follow-up period of 17 months. This study demonstrates that the extra-anatomic femoro-femoral bypass procedure is an effective alternative therapeutic modality for high-risk patients with an acceptable operative mortality (5.4%) and morbidity to improve the quality of life.

Gastrointestinal Side Effects of Antiarrhythmic Medications: A Review of Current Literature.

PubMed

Amjad, Waseem; Qureshi, Waqas; Farooq, Ali; Sohail, Umair; Khatoon, Salma; Pervaiz, Sarah; Narra, Pratyusha; Hasan, Syeda M; Ali, Farman; Ullah, Aman; Guttmann, Steven

2017-09-03

Antiarrhythmic drugs are commonly prescribed cardiac drugs. Due to their receptor mimicry with several of the gastrointestinal tract receptors, they can frequently lead to gastrointestinal side effects. These side effects are the most common reasons for discontinuation of these drugs by the patients. Knowledge of these side effects is important for clinicians that manage antiarrhythmic drugs. This review focuses on the gastrointestinal side effects of these drugs and provides a detailed up-to-date literature review of the side effects of these drugs. The review provides case reports reported in the literature as well as possible mechanisms that lead to gastrointestinal side effects.

Memory for Medication Side Effects in Younger and Older Adults: The Role of Subjective and Objective Importance

PubMed Central

Friedman, Michael C.; McGillivray, Shannon; Murayama, Kou; Castel, Alan D.

2014-01-01

Older adults often experience memory impairments, but can sometimes use selective processing and schematic support to remember important information. The current experiments investigate to what degree younger and healthy older adults remember medication side effects that were subjectively or objectively important to remember. Participants studied a list of common side effects, and rated how negative these effects were if they were to experience them, and were then given a free recall test. In Experiment 1, the severity of the side effects ranged from mild (e.g., itching) to severe (e.g., stroke), and in Experiment 2, certain side effects were indicated as critical to remember (i.e., “contact your doctor if you experience this”). There were no age differences in terms of free recall of the side effects, and older adults remembered more severe side effects relative to mild effects. However, older adults were less likely to recognize critical side effects on a later recognition test, relative to younger adults. The findings suggest that older adults can selectively remember medication side effects, but have difficulty identifying familiar but potentially critical side effects, and this has implications for monitoring medication use in older age. PMID:25331278

Women's interpretation of and responses to potential gynaecological cancer symptoms: a qualitative interview study

PubMed Central

Low, E L; Whitaker, K L; Simon, A E; Sekhon, M; Waller, J

2015-01-01

Objective To explore women's experiences of symptoms potentially indicative of gynaecological cancer in a community-based sample without imposing a cancer perspective. Design A qualitative interview study with thematic analysis of transcripts. Participants 26 women aged ≥30 years, who had experienced a symptom that might indicate gynaecological cancer in the past 3 months, were recruited using a screening questionnaire distributed online and in community settings. Setting London, UK. Results Women attributed gynaecological symptoms to existing illnesses/conditions or considered themselves to be predisposed to them, either through their ‘genes’ or previous personal experience. Normalising symptoms by attributing them to demographic characteristics (eg, age, sex) was common, as was considering them a side effect of hormonal contraception. When women raised cancer as a possible cause, they often dismissed it as unlikely. Responses to symptoms included self-management (eg, self-medicating, making lifestyle changes), adopting a ‘lay system of care’, or consulting a healthcare professional. Triggers to help-seeking included persistent, painful or debilitating symptoms, concern about symptom seriousness, and feeling that help-seeking was legitimised. Barriers to help-seeking included lack of concern, vague symptoms, unusual symptom location, competing time demands, previous negative experiences with the healthcare system, and not wanting to be perceived as a time-waster. Conclusions Attributions of symptoms potentially indicative of a gynaecological cancer were varied, but most often involved women fitting symptoms into their expectations of what was ‘normal’. Normalising acted as a barrier to seeking help from a healthcare professional, alongside competing time demands and negative attitudes towards help-seeking. These barriers may lead to later diagnosis and poorer cancer survival. Our findings could be used to inform the development of interventions to encourage appropriate help-seeking. PMID:26150145

Platelet-rich plasma treatment improves outcomes for chronic proximal hamstring injuries in an athletic population.

PubMed

Fader, Ryan R; Mitchell, Justin J; Traub, Shaun; Nichols, Roger; Roper, Michelle; Mei Dan, Omer; McCarty, Eric C

2014-01-01

chronic proximal hamstring tendinopathies is a disabling activity related condition. Currently, there is no well-accepted or extensively documented non-operative treatment option that provides consistently successful results. to evaluate the efficacy of ultrasound guided platelet-rich plasma injections in treating chronic proximal hamstring tendinopathies. a total of 18 consecutive patients were retrospectively analyzed. All patients received a single injection of platelet rich plasma via ultra-sound guidance by a single radiologist. Outcome measures included a questionnaire evaluating previous treatments, visual analog scale (VAS) for pain, subjective improvement, history of injury, and return to activity. the patient population included 12 females and 6 males. The average age at the time of the injection was 42.6 years (19-60). Provocative activities included running, biking, swimming. The average body mass index of patients was 22.9 (17.2-30.2). The average time of chronic pain prior to receiving the first injection was 32.6 months (6-120). All patients had attempted other forms of non-surgical treatment prior to entering the study. The average VAS pre-injection was 4.6 (0-8). Six months after the injection, 10/18 patients had 80% or greater improvement in their VAS. Overall, the average improvement was 63% (5-100). The only documented side effect was post-injection discomfort that resolved within seventy-two hours. chronic hamstring tendinopathy is a debilitating condition secondary to the pain, which limits an athlete's ability to perform. For refractory cases of chronic insertional proximal hamstring injuries, platelet-rich plasma injections are safe and show benefit in the majority of patients in our study, allowing return to pre-injury activities. Case series; Level of evidence, 4.

Platelet-rich plasma treatment improves outcomes for chronic proximal hamstring injuries in an athletic population

PubMed Central

Fader, Ryan R.; Mitchell, Justin J.; Traub, Shaun; Nichols, Roger; Roper, Michelle; Mei Dan, Omer; McCarty, Eric C.

2014-01-01

Summary Background: chronic proximal hamstring tendinopathies is a disabling activity related condition. Currently, there is no well-accepted or extensively documented non-operative treatment option that provides consistently successful results. Purpose: to evaluate the efficacy of ultrasound guided platelet-rich plasma injections in treating chronic proximal hamstring tendinopathies. Methods: a total of 18 consecutive patients were retrospectively analyzed. All patients received a single injection of platelet rich plasma via ultra-sound guidance by a single radiologist. Outcome measures included a questionnaire evaluating previous treatments, visual analog scale (VAS) for pain, subjective improvement, history of injury, and return to activity. Results: the patient population included 12 females and 6 males. The average age at the time of the injection was 42.6 years (19–60). Provocative activities included running, biking, swimming. The average body mass index of patients was 22.9 (17.2–30.2). The average time of chronic pain prior to receiving the first injection was 32.6 months (6–120). All patients had attempted other forms of non-surgical treatment prior to entering the study. The average VAS pre-injection was 4.6 (0–8). Six months after the injection, 10/18 patients had 80% or greater improvement in their VAS. Overall, the average improvement was 63% (5–100). The only documented side effect was post-injection discomfort that resolved within seventy-two hours. Conclusion: chronic hamstring tendinopathy is a debilitating condition secondary to the pain, which limits an athlete’s ability to perform. For refractory cases of chronic insertional proximal hamstring injuries, platelet-rich plasma injections are safe and show benefit in the majority of patients in our study, allowing return to pre-injury activities. Study Design: Case series; Level of evidence, 4. PMID:25767784

Swallowing outcome measures in head and neck cancer--How do they compare?

PubMed

Pedersen, A; Wilson, Janet; McColl, Elaine; Carding, Paul; Patterson, Jo

2016-01-01

Dysphagia is a common and debilitating side effect of chemoradiotherapy. Assessment is difficult; swallowing is multifactorial and studies choose from a range of dysphagia assessments. This study intended to investigate the relationship between swallowing assessments of dysphagia in a cohort of patients and to evaluate whether clinical swallowing measures can predict patient reported swallowing outcomes. One hundred and seventy-three head and neck cancer patients from two teaching hospitals were recruited prospectively over 25 months. At three months follow-up patients were assessed using Rosenbeck's Penetration-Aspiration Scale (PAS), The 100 ml Water Swallow Test (WST), The Performance Status Scale: Normalcy of Diet and the MD Anderson Dysphagia Inventory (MDADI). The highest correlation was observed between the MDADI and Normalcy of Diet (rho 0.68) and the lowest between the MDADI and the PAS (rho 0.34). Using multiple regression the PAS and WST accounted for 44% of the variance in the MDADI scores (R2 = 0.44, F = 37.8, p < 0.001). On stepwise regression, the model only retained the Normalcy of Diet scores (R2 = 0.42, F=107.9, p < 0.001). Separating the PAS into subgroups, those with no penetration or aspiration on the PAS scored significantly higher on the MDADI (p = <0.001). Patient reported swallowing outcomes were strongly aligned with diet restrictions but poorly aligned with clinical assessment. The WST, however, was more correlated than the PAS score, representing a more functional assessment. Clinical dysphagia, associated with significant morbidity, and patient reported dysphagia related to quality of life are not interchangeable and must be measured separately. Copyright © 2015 Elsevier Ltd. All rights reserved.

α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

PubMed Central

Wonnacott, Susan

2011-01-01

Parkinson's disease is a debilitating movement disorder characterized by a generalized dysfunction of the nervous system, with a particularly prominent decline in the nigrostriatal dopaminergic pathway. Although there is currently no cure, drugs targeting the dopaminergic system provide major symptomatic relief. As well, agents directed to other neurotransmitter systems are of therapeutic benefit. Such drugs may act by directly improving functional deficits in these other systems, or they may restore aberrant motor activity that arises as a result of a dopaminergic imbalance. Recent research attention has focused on a role for drugs targeting the nicotinic cholinergic systems. The rationale for such work stems from basic research findings that there is an extensive overlap in the organization and function of the nicotinic cholinergic and dopaminergic systems in the basal ganglia. In addition, nicotinic acetylcholine receptor (nAChR) drugs could have clinical potential for Parkinson's disease. Evidence for this proposition stems from studies with experimental animal models showing that nicotine protects against neurotoxin-induced nigrostriatal damage and improves motor complications associated with l-DOPA, the “gold standard” for Parkinson's disease treatment. Nicotine interacts with multiple central nervous system receptors to generate therapeutic responses but also produces side effects. It is important therefore to identify the nAChR subtypes most beneficial for treating Parkinson's disease. Here we review nAChRs with particular emphasis on the subtypes that contribute to basal ganglia function. Accumulating evidence suggests that drugs targeting α6β2* and α4β2* nAChR may prove useful in the management of Parkinson's disease. PMID:21969327

Footwear width and balance-recovery reactions: A new approach to improving lateral stability in older adults

PubMed Central

Yamaguchi, Takeshi; Cheng, Kenneth C.; McKay, Sandra M.; Maki, Brian E.

2016-01-01

Background Age-related difficulty in controlling lateral stability is of crucial importance because lateral falls increase risk of debilitating hip-fracture injury. This study examined whether a small increase in footwear sole width can improve ability of older adults to regain lateral stability subsequent to balance perturbation. Methods The study involved sixteen healthy, ambulatory, community-dwelling older adults (aged 65–78). Widened base-of-support (WBOS) footwear was simulated by affixing polystyrene-foam blocks (20mm wide) on the medial and lateral sides of rubber overshoes; unaltered overshoes were worn in normal (NBOS) trials. Balance perturbations were applied using a motion platform. Results Gait, mobility and agility tests revealed no adverse effects of wearing the WBOS footwear. Lateral-perturbation tests showed that the WBOS footwear improved ability to stabilize the body without stepping (p=0.002). Depending on the perturbation magnitude, the frequency of stepping was reduced by up to 25% (64% of NBOS trials vs 39% of WBOS trials). In addition, the WBOS footwear appeared to improve ability to maintain lateral stability during forward-step reactions, as evidenced by reduced incidence of additional lateral steps (p=0.04) after stepping over an obstacle in response to a forward-fall perturbation. Conclusions A small increase in sole width can improve certain aspects of lateral stability in older adults, without compromising mobility and agility. This finding supports the viability of WBOS footwear as an intervention to improve balance. Further research is needed to test populations with more severe balance impairments, examine user compliance, and determine if WBOS footwear actually reduces falling risk in daily life. PMID:27099603

Perinatal Generalized Anxiety Disorder: Assessment and Treatment

PubMed Central

Abizadeh, Jasmin; Sanders, Shawn; Swift, Elena

2015-01-01

Abstract Perinatal generalized anxiety disorder (GAD) has a high prevalence of 8.5%–10.5% during pregnancy and 4.4%–10.8% postpartum. Despite its attendant dysfunction in the patient, this potentially debilitating mental health condition is often underdiagnosed. This overview will provide guidance for clinicians in making timely diagnosis and managing symptoms appropriately. A significant barrier to the diagnosis of GAD in the perinatal population is difficulty in distinguishing normal versus pathological worry. Because a perinatal-specific screening tool for GAD is nonexistent, early identification, diagnosis and treatment is often compromised. The resultant maternal dysfunction can potentially impact mother–infant bonding and influence neurodevelopmental outcomes in the children. Comorbid occurrence of GAD and major depressive disorder changes the illness course and its treatment outcome. Psychoeducation is a key component in overcoming denial/stigma and facilitating successful intervention. Treatment strategies are contingent upon illness severity. Cognitive behavior therapy (CBT), relaxation, and mindfulness therapy are indicated for mild GAD. Moderate/severe illness requires pharmacotherapy and CBT, individually or in combination. No psychotropic medications are approved by the FDA or Health Canada in pregnancy or the postpartum; off-label pharmacological treatment is instituted only if the benefit of therapy outweighs its risk. SSRIs/SNRIs are the first-line treatment for anxiety disorders due to data supporting their efficacy and overall favorable side effect profile. Benzodiazepines are an option for short-term treatment. While research on atypical antipsychotics is evolving, some can be considered for severe manifestations where the response to antidepressants or benzodiazepines has been insufficient. A case example will illustrate the onset, clinical course, and treatment strategies of GAD through pregnancy and the postpartum. PMID:26125602

21 CFR 520.1870 - Praziquantel tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

... debilitated animals and for assistance in the diagnosis, treatment, and control of parasitism. (B) If labeled..., treatment, and control of parasitism. [46 FR 60570, Dec. 11, 1981, as amended at 47 FR 26377, June 18, 1982...

21 CFR 522.1335 - Medetomidine hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... solution contains 1.0 milligram of medetomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of... diseases, dogs in shock, dogs which are severly debilitated, or dogs which are stressed due to extreme heat...

21 CFR 522.1335 - Medetomidine hydrochloride injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... solution contains 1.0 milligram of medetomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of... diseases, dogs in shock, dogs which are severly debilitated, or dogs which are stressed due to extreme heat...

21 CFR 522.1335 - Medetomidine hydrochloride injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... solution contains 1.0 milligram of medetomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of... diseases, dogs in shock, dogs which are severly debilitated, or dogs which are stressed due to extreme heat...

21 CFR 522.1335 - Medetomidine hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... solution contains 1.0 milligram of medetomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of... diseases, dogs in shock, dogs which are severly debilitated, or dogs which are stressed due to extreme heat...

“So far it’s been choosing which side effects I want or I can deal with”: A grounded theory of HIV treatment side effects among people living with HIV

PubMed Central

Holmes, Dave

2016-01-01

Despite the availability of new antiretroviral drugs and the simplification of treatment options, side effects continue to affect people living with HIV. In this paper, we present the findings of a grounded theory study designed to gain a critical understanding of the experience of side effects. Three main categories emerged from the data: the side effects, the experience, and the connections. The first category suggests that we need to change how we think about side effects in order to take into account the context in which they are experienced as well as the types and nature of side effects. The second category puts forward the idea that the experience of side effects is composed of three interrelated processes: becoming with, living with, and dealing with. Finally, the third category points to new connections that are formed with people, things and systems in the presence of side effects. PMID:27867446

Relation between therapeutic response and side effects induced by methylphenidate as observed by parents and teachers of children with ADHD.

PubMed

Lee, James; Grizenko, Natalie; Bhat, Venkataramana; Sengupta, Sarojini; Polotskaia, Anna; Joober, Ridha

2011-04-21

The desired (therapeutic) and undesired (side) effects of methylphenidate might have underlying correlations. The aim of this study was to explore the strength and the possible sources of these correlations. One hundred and fifty-seven children with ADHD (6-12 years) were administered placebo and methylphenidate (0.5 mg/kg in a divided b.i.d. dose), each for a one-week period, in a double-blind, crossover trial. Therapeutic response was assessed using the Conners' Global Index for parents (CGI-Parents) and teachers (CGI-Teachers), while side effects were assessed using the Barkley Side Effects Rating Scale (SERS). The side effect profile as assessed by the SERS was similar to that of previous studies with insomnia, decreased appetite, and headaches showing significant treatment effects (p < 0.005). These "somatic/physical" side effects did not correlate with CGI-Parents or CGI-Teachers. However, the side effects of "irritability", "proneness to crying", and "anxiousness" showed significant relationships with CGI-Parents. These "mood/anxiety" side effects showed no significant correlations with the CGI-Teachers. The greater "mood/anxiety" side effects on methylphenidate and placebo, the less the parents observe improvement of their children while treated with methylphenidate. This suggests that the correlations between "mood/anxiety" side effects and poor response to treatment may be driven by observer effects rather than biological commonalities between therapeutic and side effects of methylphenidate.

Side Effects

Cancer.gov

Side effects are problems that occur when cancer treatment affects healthy tissues or organs. Learn about side effects caused by cancer treatment. Know what signs and symptoms to call your doctor about. Learn about treatments for side effects.

Treating inflammatory bowel disease by adsorptive leucocytapheresis: a desire to treat without drugs.

PubMed

Saniabadi, Abbi R; Tanaka, Tomotaka; Ohmori, Toshihide; Sawada, Koji; Yamamoto, Takayuki; Hanai, Hiroyuki

2014-08-07

Ulcerative colitis and Crohn's disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients' own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients' disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much favoured by patients for its good safety profile. GMA in 21st century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs.

Treating inflammatory bowel disease by adsorptive leucocytapheresis: A desire to treat without drugs

PubMed Central

Saniabadi, Abbi R; Tanaka, Tomotaka; Ohmori, Toshihide; Sawada, Koji; Yamamoto, Takayuki; Hanai, Hiroyuki

2014-01-01

Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients’ own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients’ disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much favoured by patients for its good safety profile. GMA in 21st century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs. PMID:25110409

Blockade of the spinal BDNF-activated JNK pathway prevents the development of antiretroviral-induced neuropathic pain.

PubMed

Sanna, Maria Domenica; Ghelardini, Carla; Galeotti, Nicoletta

2016-06-01

Although antiretroviral agents have been used successfully in suppressing viral production, they have also been associated with a number of side effects. The antiretroviral toxic neuropathy induces debilitating and extremely difficult to treat pain syndromes that often lead to discontinuation of antiretroviral therapy. Due to the critical need for the identification of novel therapeutic targets to improve antiretroviral neuropathic pain management, we investigated the role of the JNK signalling pathway in the mechanism of antiretroviral painful neuropathy. Mice were exposed to zalcitabine (2',3'-dideoxycytidine, ddC) and stavudine (2',3'-didehydro-3'-deoxythymidine, d4T) that induced a persistent mechanical allodynia and a transient cold allodynia. Treatment with the JNK blocker SP600125 before antiretroviral administration abolished mechanical hypersensitivity with no effect on thermal response. A robust spinal JNK overphosphorylation was observed on post-injection day 1 and 3, along with a JNK-dependent increase in p-c-Jun and ATF3 protein levels. Co-immunoprecipitation experiments showed the presence of a heterodimeric complex between ATF3 and c-Jun indicating that these transcription factors can act together to regulate transcription through heterodimerization. A rise in BDNF and caspase-3 protein levels was detected on day 1 and BDNF sequestration prevented both caspase-3 and p-JNK increase. These data suggest that BDNF plays a role in the early stages of ddC-induced allodynia by promoting apoptotic events and the activation of a hypernociceptive JNK-mediated pathway. We illustrated the activation of a BDNF-mediated JNK pathway involved in the early events responsible for the promotion of neuropathic pain, leading to a better knowledge of the mechanisms involved in the antiretroviral neuropathy. JNK blockade prevents antiretroviral-induced pain hypersensitivity. This may represent a potential prophylactic treatment of neuropathic pain to improve antiretroviral tolerability. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effect of a supersaturated calcium phosphate mouth rinse on the development of oral mucositis in head and neck cancer patients treated with (chemo)radiation: a single-center, randomized, prospective study of a calcium phosphate mouth rinse + standard of care versus standard of care.

PubMed

Lambrecht, Maarten; Mercier, Carole; Geussens, Yasmyne; Nuyts, Sandra

2013-10-01

Mucosal damage is an important and debilitating side effect when treating head and neck cancer patients with (chemo-)radiation. The aim of this randomized clinical trial was to investigate whether the addition of a neutral, supersaturated, calcium phosphate (CP) mouth rinse benefits the severity and duration of acute mucositis in head and neck cancer patients treated with (chemo)radiation. A total of 60 patients with malignant neoplasms of the head and neck receiving (chemo)radiation were included in this study. Fifty-eight patients were randomized into two treatment arms: a control group receiving standard of care (n = 31) and a study group receiving standard of care + daily CP mouth rinses (n = 27) starting on the first day of (chemo-)radiation. Oral mucositis and dysphagia were assessed twice a week using the National Cancer Institute common toxicity criteria scale version 3, oral pain was scored with a visual analogue scale. No significant difference in grade III mucositis (59 vs. 71 %; p = 0.25) and dysphagia (33 vs. 42 %, p = 0.39) was observed between the study group compared to the control group. Also no significant difference in time until development of peak mucositis (28.6 vs. 28.7 days; p = 0.48), duration of peak mucositis (22.7 vs. 24.6 days; p = 0.31), recuperation of peak dysphagia (20.5 vs 24.2 days; p = 0.13) and occurrence of severe pain (56 vs. 52 %, p = 0.5). In this randomized study, the addition of CP mouth rinse to standard of care did not improve the frequency, duration or severity of the most common acute toxicities during and early after (chemo)radiation. There is currently no evidence supporting its standard use in daily practice.

Side Effects of HIV Medicines: HIV and Lactic Acidosis

MedlinePlus

... Drugs Clinical Trials Apps skip to content Side Effects of HIV Medicines Home Understanding HIV/AIDS Fact ... and Immunizations What is a Drug Interaction? Side Effects of HIV Medicines HIV Medicines and Side Effects ...

Framing effects on expectations, decisions, and side effects experienced: the case of influenza immunization.

PubMed

O'Connor, A M; Pennie, R A; Dales, R E

1996-11-01

To examine the effects of using positive or negative frames to describe influenza vaccine benefits and side effects on patients' expectations, decisions, decisional conflict, and reported side effects. 292 previously unimmunized patients with chronic respiratory or cardiac disease were randomly assigned to receive benefit/risk information that was framed: (1) positively as the percentage who remain free of influenza and have no vaccine side effects, or (2) negatively as the percentage who acquire influenza and have vaccine side effects. Questionnaires elicited expectations, decisions, and decisional conflict. Vaccines were telephoned 3 days later for a self-report of local and systemic side effects and work absenteeism. Both groups had similar immunization rates and decisional conflict scores. The positive frame group had lower and more realistic expectations of vaccine side effects, fewer systemic side effects, and less work absenteeism (p < 0.05). In contrast to previous studies of health care workers, framing did not influence patients' decisions, possibly due to the patients' awareness of their higher risk of influenza complications and greater desire to follow recommendations. The common practice of using negative frames when describing probabilities of side effects may need to be reexamined, considering its deleterious influence on self-reported side effects and work absenteeism.

Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children.

PubMed

Erdem, Semiha Bahceci; Nacaroglu, Hikmet Tekin; Unsal Karkiner, Canan Sule; Gunay, Ilker; Can, Demet

2015-10-01

Leukotriene receptor antagonists (LTRAs) are drugs which have been widely used more than ten years. As the use of LTRAs increases, our knowledge with respect to their side effects increases as well. The objective of our study was to evaluat the observed side effects of LTRAs used in patients with astma. 1024 patients treated only with LTRAs owing to asthma or early wheezing were included in the study for a five-year period. The observed side effects of LTRAs in these patients were retrospectively investigated. The side effects were divided into two parts as psychiatric and non-psychiatric. Among the 1024 cases included in the study, 67.5% of the patients out of 41 with side effects were male, 32.5% were female and the average age was 6.5 years. The rate of patients with asthma was 63.41% and 36.58% of the patients had early wheezing. It was determined that sex, age and diagnosis (early wheezing or asthma) of the patients were ineffective in the emergence of side effects. The average period for the emergence of side effects was the first month. It was observed that hyperactivity was the most frequently observed psychiatric side effect and that abdominal pain was the non-psychiatric side effect. The side effects of LTRAs were common in children. Therefore, patients must be informed at the beginning of the treatment and they must be evaluated at certain intervals.

Denying Sanctuary

DTIC Science & Technology

2009-04-01

the socio-economic conditions, the most debilitating of which was “economic maladjustment ,” 34 were pathetic. The Algerian economy was primarily...representation, economic maladjustment and poor standards of living caused by lack of essential services disenfranchised the native Algerian populace. In

Defining sarcopenia

USDA-ARS?s Scientific Manuscript database

Currently there is no standardized definition of sarcopenia. This hampers the clinical management of sarcopenia and retards the development and regulatory approval of interventions to reduce the progression of this common and debilitating condition in the elderly. Nine definitions of sarcopenia have...

A Comparison of Sexual Side Effects of Antidepressants With and Without Naltrexone.

PubMed

Thapa, Mona; Petrakis, Ismene; Ralevski, Elizabeth

2017-01-01

The aim of the study was to compare the rate of sexual side effects of the selective serotonin reuptake inhibitor paroxetine versus the tricyclic antidepressant desipramine and to examine the effect of co-prescription of naltrexone on sexual side effects among participants in a randomized clinical trial. This was a secondary analysis (N = 88) of veterans who participated in a 12-week trial. All veterans were randomized into one of four treatment groups: (a) desipramine/naltrexone, (b) desipramine/placebo, (c) paroxetine/naltrexone, and (d) paroxetine/placebo. The main outcome measure was the frequency of sexual side effects consisting of "decreased sex drive" and/or "impotence" reported by veterans at each weekly visit. Approximately 61% of the veterans reported sexual side effects at least once during the trial, and 26.4% reported sexual side effects throughout the study. There were no significant differences in the frequency of sexual side effects among the four treatment groups. The results were similar when the comparison was made between the two antidepressant groups. There were no significant differences in the reporting of sexual side effects between those receiving desipramine and paroxetine. Also, the comparison between naltrexone and placebo did not alter the results. This is the first study to compare frequency of sexual side effect reporting between paroxetine and desipramine. We found no statistically significant differences in sexual side effect reporting between the two antidepressants. Also, the addition of naltrexone did not show any beneficial effect on the sexual side effect profile.

Development and Validity of Western University's On-Road Assessment.

PubMed

Classen, Sherrilene; Krasniuk, Sarah; Alvarez, Liliana; Monahan, Miriam; Morrow, Sarah A; Danter, Tim

2017-01-01

Although used across North America, many on-road studies do not explicitly document the content and metrics of on-road courses and accompanying assessments. This article discusses the development of the University of Western Ontario's on-road course, and elucidates the validity of its accompanying on-road assessment. We identified main components for developing an on-road course and used measurement theory to establish face, content, and initial construct validity. Five adult volunteer drivers and 30 drivers with multiple sclerosis participated in the study. The road course had face and content validity, representing 100% of roadway components determined through a content validity matrix and index. The known-groups method showed that debilitated drivers (vs. not debilitated), made more driving errors ( W = 463.50, p = .03), and failed the on-road course, indicating preliminary construct validity of the on-road assessment. This research guides and empirically supports a process for developing a road course and its assessment.

Evaluation of Therapeutics for Advanced-Stage Heart Failure and Other Severely-Debilitating or Life-Threatening Diseases.

PubMed

Prescott, J S; Andrews, P A; Baker, R W; Bogdanffy, M S; Fields, F O; Keller, D A; Lapadula, D M; Mahoney, N M; Paul, D E; Platz, S J; Reese, D M; Stoch, S A; DeGeorge, J J

2017-08-01

Severely-debilitating or life-threatening (SDLT) diseases include conditions in which life expectancy is short or quality of life is greatly diminished despite available therapies. As such, the medical context for SDLT diseases is comparable to advanced cancer and the benefit vs. risk assessment and development of SDLT disease therapeutics should be similar to that of advanced cancer therapeutics. A streamlined development approach would allow patients with SDLT conditions earlier access to therapeutics and increase the speed of progression through development. In addition, this will likely increase the SDLT disease therapeutic pipeline, directly benefiting patients and reducing the economic and societal burden of SDLT conditions. Using advanced-stage heart failure (HF) as an example that illustrates the concepts applicable to other SDLT indications, this article proposes a streamlined development paradigm for SDLT disease therapeutics and recommends development of aligned global regulatory guidance. © 2017 American Society for Clinical Pharmacology and Therapeutics.

How does the side-effect information in patient information leaflets influence peoples' side-effect expectations? A cross-sectional national survey of 18- to 65-year-olds in England.

PubMed

Webster, Rebecca K; Weinman, John; Rubin, G James

2017-12-01

To establish how the terms recommended by the European Commission to describe side-effect risk in patient information leaflets (PILs) influences expectations of side-effects and to identify factors associated with these side-effect expectations. A cross-sectional online survey was carried out by a market research company. Data were collected in England between 18th March and 1st April 2016. A total of 1003 adults aged between 18 and 65. Self-reported expectation that the described side-effects would affect participants if they took the medicine, measured on a likelihood scale from 1 (very unlikely) to 5 (very likely). Participants formed high expectations of side-effects for "very common" and "common" side-effects, with 51.9% and 45.0% of participants rating these as "very likely" or "likely" to happen to them, respectively. This fell to 8.1% for "uncommon," 5.8% for "rare" and 4.1% for "very rare." For each descriptor, higher expectations of side-effects were more associated with women or being from an ethnic minority, or having less education, a household illness, high perceived sensitivity to medicines or negative beliefs about medicines. The current use of verbal descriptors to communicate side-effect risk in PILs leads to high side-effect expectations. These expectations could contribute to nocebo-induced medication side-effects experienced by patients. Additional work is required to identify ways to improve the way risk information is conveyed in PILs. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

Treatment of Chlamydia-associated ocular disease via a recombinant protein based vaccine in the koala (Phascolarctos cinereus).

PubMed

Waugh, Courtney; Austin, Ray; Polkinghorne, Adam; Timms, Peter

2016-11-01

Koalas (Phascolarctos cinereus) are affected by debilitating chlamydial disease that can lead to blindness, infertility, and death. The causative agent is the intracellular bacterium Chlamydia pecorum. While antibiotics can be used to treat koala chlamydial infection, they are often ineffective or cause severe dysbiosis to the animal's unique gut flora. Recent work has progressed on the development of a protective vaccine for Chlamydia in the koala. This study demonstrates that the use of a vaccine can have a positive effect in koalas already with clinical signs of ocular disease, suggesting a possible therapeutic effect and an alternative to antibiotic therapy. Copyright © 2016 International Alliance for Biological Standardization. All rights reserved.

Wernicke-Korsakoff syndrome: recognition and treatment.

PubMed

Donnelly, Alexander

2017-03-29

Wernicke-Korsakoff syndrome is a potentially debilitating and fatal condition that is caused by thiamine (vitamin B1) deficiency in the brain. It can be treated effectively or prevented completely; however, the condition is often undiagnosed and inadequately managed. Wernicke-Korsakoff syndrome is commonly considered to be specific to individuals who misuse alcohol; however, there are many other predisposing factors and causes associated with the condition. This article aims to raise awareness of Wernicke-Korsakoff syndrome, to enable nurses in all practice settings to recognise the signs, symptoms and risk factors associated with the condition and be informed about available treatments. Increased awareness aims to improve early diagnosis of the condition, enabling effective treatment and improving patients' symptoms, such as cognitive impairment.

Side Effects to Antidepressant Treatment in Patients With Depression and Comorbid Panic Disorder.

PubMed

Shankman, Stewart A; Gorka, Stephanie M; Katz, Andrea C; Klein, Daniel N; Markowitz, John C; Arnow, Bruce A; Manber, Rachel; Rothbaum, Barbara O; Thase, Michael E; Schatzberg, Alan F; Keller, Martin B; Trivedi, Madhukar H; Kocsis, James H

2017-04-01

Side effects to antidepressant medication can affect the efficacy of treatment, but few predictors foretell who experiences side effects and which side effects they experience. This secondary data analysis examined whether depressed patients with comorbid panic disorder were more likely to experience side effects than those without panic disorder. The study also examined whether greater burden of side effects predicted a poorer treatment course for patients with panic disorder than those without panic disorder. To examine the specificity of these effects, analyses also examined 2 other anxiety disorders-social phobia and generalized anxiety disorder (GAD). Between 2002 and 2006, a large sample (N = 808) of chronically depressed individuals (assessed using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders [SCID-IV]) received antidepressants according to a predetermined algorithm for 12 weeks. Every 2 weeks, depressive symptoms (per the Hamilton Depression Rating Scale) and side effects (specific side effects as well as several indicators of side effect burden) were assessed. Lifetime diagnosis of panic disorder (assessed using the SCID-IV) at baseline was associated with higher likelihood of gastrointestinal (OR = 1.6 [95% CI, 1.0-2.6]), cardiac (OR = 1.8 [95% CI, 1.1-3.1]), neurologic (OR = 2.6 [95% CI, 1.6-4.2]), and genitourinary side effects (OR = 3.0 [95% CI, 1.7-5.3]) during treatment. Increases in side effect frequency, intensity, and impairment over time were more strongly associated with increases in depressive symptoms for patients with panic disorder compared to those without panic disorder. Neither social phobia nor GAD was associated with these effects. Potentially due to heighte​ned interoceptive awareness of changes in their body, chronically depressed individuals with panic disorder may be at greater risk than those without panic disorder for antidepressant side effects and to experience a worsening of depressive symptoms as a result of these side effects over time. ClinicalTrials.gov identifier: NCT00057551​. © Copyright 2017 Physicians Postgraduate Press, Inc.

Medications and Side Effects

MedlinePlus

... to fully work. You might feel some side effects of your medication before your feel the benefits – ... as sleepiness, anxiety or headache) is a side effect or a symptom of your illness. Many side ...

Cancer Treatment for Women: Possible Sexual Side Effects

MedlinePlus

... the clitoris. These play a major part in sexual arousal in women. Removing the vulva and the clitoris ... www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/fertility-and-sexual-side-effects/sexuality-for-women-with-cancer.html. ...

"There is a chain of connections": using syndemics theory to understand HIV treatment side effects.

PubMed

Gagnon, Marilou

2018-03-12

Side effects are central to the experience of living longer with HIV but rarely have they been studied alone. Unlike other aspects of that experience, like quality of life, treatment adherence, chronicity, episodic disability, aging, health, and viral load suppression, side effects have not benefited from the same level of empirical and theoretical engagement from qualitative researchers. In this paper, we draw on syndemics theory and 50 qualitative interviews to better understand the experience of HIV treatment side effects. Two main categories were identified in the data: side effects as a product and side effects as a risk factor. The first category suggests that side effects are not just the product of taking antiretroviral drugs. They are also the product of particular conditions and tend to cluster with other health problems. The second category puts forward the idea that side effects can act as a syndemic risk factor by exposing PLWH to a greater risk of developing health problems and creating conditions in which psychosocial issues are more likely to emerge. The paper concludes by calling for more research on the complex nature of side effects and for the development of comprehensive approaches for the assessment and management of side effects.

Patient-provider communication and hormonal therapy side effects in breast cancer survivors.

PubMed

Lin, Jenny J; Chao, Jennifer; Bickell, Nina A; Wisnivesky, Juan P

2017-09-01

Side effects from hormonal therapy (HT) for breast cancer treatment occur frequently and are associated with worse quality of life and HT non-adherence. Whether improved patient-physician communication is associated with patients' reporting of side effects is unknown. We undertook this study to assess factors associated with women's reports of HT side effects. Between December 2012 and April 2013, we conducted a cross-sectional survey of breast cancer patients undergoing HT in an urban medical center. Descriptive statistics, univariate analyses, and multivariate analyses were used to evaluate associations. Of the 100 participants, 67% reported having HT side effects. However, when prompted, an additional 9% reported experiencing specific HT-related symptoms. Despite very high communication scores, one-third of participants reported they had not discussed side effects with providers. Multivariate analysis showed that after controlling for age, education, race, and medication beliefs, women who had difficulty asking providers for more information were more likely to report side effects (odds ratio 8.27, 95% confidence interval 1.01-69.88). Although HT side effects often occur and are bothersome, patient-provider discussions about side effects remain suboptimal. Providers should actively ask patients about medication side effects so that they can be addressed to improve quality of life and potentially, medication adherence.

Chronic debilitating fatigue in Irish general practice: a survey of general practitioners' experience.

PubMed

Fitzgibbon, E J; Murphy, D; O'Shea, K; Kelleher, C

1997-10-01

Doctors are called upon to treat chronic debilitating fatigue without the help of a protocol of care. To estimate the incidence of chronic debilitating fatigue in Irish general practice, to obtain information on management strategy and outcome, to explore the attitudes of practitioners (GPs) towards the concept of a chronic fatigue syndrome (CFS), and to recruit practitioners to a prospective study of chronic fatigue in primary care. A total of 200 names were selected from the database of the Irish College of General Practitioners (ICGP); 164 of these were eligible for the study. Altogether, 118 questionnaires were returned (72%). Ninety-two (78%) responders identified cases of chronic fatigue, giving an estimated 2.1 cases per practice and an incidence of 1 per 1000 population. All social classes were represented, with a male to female ratio of 1:2. Eleven disparate approaches to treatment were advocated. Many (38%) were dissatisfied with the quality of care delivered, and 45% seldom or hardly ever referred cases for specialist opinion. The majority (58%) accepted CFS as a distinct entity, 34% were undecided, and 8% rejected it. Forty-two (35%) GPs volunteered for a prospective study. Chronic fatigue is found in Irish general practice among patients of both sexes and all social classes. Doctors differ considerably in their management of patients and are dissatisfied with the quality of care they deliver. Many cases are not referred for specialist opinion. A prospective database is required to accurately assess the scale of this public health problem and to develop a protocol of care.

Side effect burden of antipsychotic drugs in real life - Impact of gender and polypharmacy.

PubMed

Iversen, Trude Seselie Jahr; Steen, Nils Eiel; Dieset, Ingrid; Hope, Sigrun; Mørch, Ragni; Gardsjord, Erlend Strand; Jørgensen, Kjetil Nordbø; Melle, Ingrid; Andreassen, Ole A; Molden, Espen; Jönsson, Erik G

2018-03-02

Antipsychotic-associated side effects are well known and represent a significant treatment challenge. Still, few large studies have investigated the overall side effect burden of antipsychotics in real-life settings. To describe the occurrence of side effects and perceived burden of antipsychotics in a large naturalistic sample, taking polypharmacy and patient characteristics into account. Patients (n=1087) with psychotic disorders were assessed for side effects using the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale in addition to assessment of clinical and pharmacological data. Statistical analyses were performed controlling for possible confounding factors. Use of antipsychotics showed significant associations to neurologic and sexual symptoms, sedation and weight gain, and >75% of antipsychotics-users reported side effects. More side effects were observed in patients using several antipsychotics (p=0.002), with increasing total dose (p=0.021) and with antipsychotics in combinations with other psychotropic drugs. Patients and investigators evaluated the side effect burden differently, particularly related to severity, gender and antipsychotics dose. Twice as many females described side effect burden as severe (p=0.004). Patients with psychotic disorders have a high occurrence of symptoms associated with use of antipsychotics, and polypharmacy and female gender are seemingly risk factors for reporting a severe side effect burden. Due to the cross-sectional design evaluation of causality is tentative, and these findings should be further investigated in prospective studies. Copyright © 2017 Elsevier Inc. All rights reserved.

The Glasgow antipsychotic side-effects scale for clozapine in inpatients and outpatients with schizophrenia or schizoaffective disorder.

PubMed

Ignjatović Ristić, Dragana; Cohen, Dan; Obradović, Andrea; Nikić-Đuričić, Katarina; Drašković, Marija; Hinić, Darko

2018-02-01

The inconsistency in clinician and patient ratings of clozapine-induced side effects underscore the need to supplement clinician-based estimates of side effects with patient-reported ones. The main aims of the study are validation of the Glasgow antipsychotic side-effects scale for clozapine (GASS-C) in Serbian inpatients/outpatients with schizophrenia or schizo-affective disorder and recommendations for its future use, based on common and rare clozapine-associated side-effects. The GASS-C was administered to 95 outpatients/inpatients diagnosed with schizophrenia, schizoaffective, or chronic psychotic disorder. The scale showed good overall reliability, with an internal consistency coefficient of α = 0.84, an average retest coefficient of rho = 0.76, and a Spearman-Brown coefficient of validity of 0.81. Side effects were absent or mild in 64.2% of the patients, moderate in 31.6%, severe in 4.2%; 14% of the subjects considered their symptoms distressing. The most commonly reported side-effects were drowsiness, thirst, frequent urination, and dry mouth. Women reported more side effects than men, and patients not in a relationship reported significantly fewer side effects than patients in a relationship. Results indicate a weak positive correlation (rho = 0.231; p = .025) between severity of side effects and clozapine dose. The GASS-C showed good psychometric characteristics in clinical population of patients on clozapine. In future studies, clozapine serum concentrations should be measured when using the GASS-C to monitor side effects.

Learning to experience side effects after antidepressant intake - Results from a randomized, controlled, double-blind study.

PubMed

Rheker, Julia; Winkler, Alexander; Doering, Bettina K; Rief, Winfried

2017-02-01

Side effects play a key role in patients' failure to take antidepressants. There is evidence that verbal suggestions and informed consent elicit expectations that can in turn trigger the occurrence of side effects. Prior experience or learning mechanisms are also assumed to contribute to the development of side effects, although their role has not been thoroughly investigated. In this study, we examined whether an antidepressant's side effects can be learned via Pavlovian conditioning. Participants (n = 39) were randomly allocated to one of two groups and were exposed to a classical conditioning procedure. During acquisition, 19 participants received amitriptyline and 20 participants received a placebo pill. Pills were taken for four nights together with a novel-tasting drink. After a washout phase, both groups received a placebo pill together with the novel-tasting drink (evocation). Side effects were assessed via the Generic Assessment of Side Effects Scale prior to acquisition (baseline), after acquisition, and after evocation. A score of antidepressant-specific side effects was calculated. Participants taking amitriptyline reported significantly more antidepressant-specific side effects after acquisition compared to both baseline and the placebo group. After evocation, participants who underwent the conditioning procedure with amitriptyline reported significantly more antidepressant-specific side effects than those who never received amitriptyline, even though both groups received a placebo. Our results indicate that antidepressant side effects can be learned using a conditioning paradigm and evoked via a placebo pill when applied with the same contextual factors as the verum.

The association of HIV/AIDS treatment side effects with health status, work productivity, and resource use.

PubMed

daCosta DiBonaventura, Marco; Gupta, Shaloo; Cho, Michelle; Mrus, Joseph

2012-01-01

Due to stable incidence and improved survival rates, there are an increasing number of patients living with HIV/AIDS in the USA. Although highly effective, current antiretroviral therapies are associated with a variety of side effects. The role side effects play on health outcomes has not been fully examined. The current study assessed the association of medication side effects with (1) self-assessed health status; (2) work productivity and activity impairment; and (3) healthcare resource utilization. Data were from a cross-sectional patient-reported survey fielded in the USA using a dual methodology of Internet and paper questionnaires. A total of 953 patients living with HIV/AIDS who were currently taking a medication for their condition were included in the analyses. The most frequent side effects reported by patients were fatigue (70.72%), diarrhea (62.96%), insomnia (58.97%), dizziness (52.78%), neuropathy (52.68%), joint pain (52.36%), nausea (51.63%), and abdominal pain (50.37%). The presence of each side effect was associated with reduced self-assessed health status, increased productivity loss, increased activity impairment, and increased healthcare resource use. Controlling for CD4 cell counts in regression modeling did little to diminish the impact of side effects. Although not all side effects were associated with all outcomes, every side effect was associated with worse health status, some measure of increased work productivity loss, and/or some measure of increased healthcare resource use. Patients are living longer with HIV and, therefore, spending a greater length of time on treatment. The results of the current study suggest that many of these patients are experiencing a wide array of side effects from these therapies. These side effects have demonstrated a profound association with self-assessed health, work productivity, and healthcare resource use. Improved management of these side effects or development of treatments with a better side effect profile may have a substantial humanistic and economic benefit.

Decreasing the Burden of Side Effects Through Positive Message Framing: an Experimental Proof-of-Concept Study.

PubMed

Wilhelm, Marcel; Rief, Winfried; Doering, Bettina K

2018-05-21

Informing patients about treatment side effects increases the occurrence and intensity of side effects. Since the obligatory informed consent procedure in drug treatments requires transparency and nocebo research suggests that the informed consent of a drug leads to an increased occurrence of the mentioned side effects, the aim of this proof of concept study was to determine the effect of two different framings of informed consent on the occurrence, intensity, and perceived threat of side effects. Healthy male participants (n = 80) were randomized to one of two framing groups. The positive framing group was informed that the common side effect dizziness was a sign that the drug had started to work, while the neutral framing group was told that dizziness is an unpleasant but well-known side effect. Side effects were measured after the administration of metoprolol, an antihypertensive agent. Post hoc moderator analyses investigated the effect of pre-existing negative beliefs about the general harm of medication on the framing manipulation. Metoprolol-specific drug-attributed side effects were rated significantly less threatening in the positive framing group. The between-group effect size (Cohen's d) was small (d = 0.38, p = 0.049). Exploratory post hoc moderator analyses suggest that participants who believed that medication is a source of harmful effects benefited from positive framing, compared to neutral framing of drug-attributed side effects. Positive framing was partially effective in decreasing specific side effect measures, particularly among participants with a tendency to believe that medicine is harmful. Informed consent procedures should therefore be personalized, focusing on patients with negative treatment beliefs.

Combined use of alcohol and energy drinks: Dose relationship with self-reported physiological stimulation and sedation side effects.

PubMed

Droste, Nicolas; Peacock, Amy; Bruno, Raimondo; Pennay, Amy; Zinkiewicz, Lucy; Lubman, Dan I; Miller, Peter

2017-08-01

Negative physiological stimulation and sedation side effects are experienced by a significant proportion of consumers who consume alcohol mixed with energy drinks (AmED). Few studies have compared the frequency of side effects between sessions of AmED and sessions of alcohol only within-subject, and none have explored a dose relationship. Explore the occurrence of self-reported physiological stimulant and sedative side effects between sessions of AmED and alcohol only, and at varying ED dosage levels within AmED sessions. A convenience sample of 2953 residents of New South Wales, Australia completed an online survey. N=731 AmED users reported daily caffeine intake, typical alcohol and AmED consumption, and past 12-month experience of physiological stimulation and sedation side effects during AmED and alcohol only sessions. Within-subject analyses compared occurrence of side effects between session types. Hierarchical binary logistic regression analyses explored the association of ED dose during AmED sessions with the experience of physiological side effects. There were greater odds of most stimulant side effects, and lower odds of sedation side effects, during AmED sessions compared to alcohol only sessions. Compared to one ED, consumption of three or more EDs was significantly associated with the majority of both stimulant and alcohol intoxication side effects after controlling for demographics and consumption covariates. AmED is associated with perceived changes in physiological stimulant and sedation side effects of alcohol. Experience of side effects is positively associated with ED dosage. Future research should account for varying ED dosage, and reflect real world consumption levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treatment factors affecting longitudinal quality of life in new onset pediatric epilepsy.

PubMed

Modi, Avani C; Ingerski, Lisa M; Rausch, Joseph R; Glauser, Tracy A

2011-05-01

Recognizing the importance of patient-reported outcomes, this longitudinal, prospective study examined: Changes in health-related quality of life (HRQOL) over seven months following antiepileptic drug (AED) initiation and the relationship of seizures, AED side-effects, and AED type to HRQOL. Parents of 124 children with newly diagnosed epilepsy completed measures of HRQOL and side-effects at each clinic visit. Treatment information was also collected. HRQOL remained stable over time; however, seizures and AED side-effects significantly affected multiple HRQOL domains. Higher seizure activity was associated with decreased Physical HRQOL. Side-effects were negatively associated with all HRQOL domains. Children taking carbamazepine who experienced higher side-effects early in therapy demonstrated declining emotional functioning compared to children experiencing no/some side-effects. AED side-effects, AED type, and seizure frequency were associated with longitudinal HRQOL in children with newly-diagnosed epilepsy. Routine assessment of AED side-effects and HRQOL may be useful for clinical decision making.

[Treatment side effects and compliance in patients with depression].

PubMed

Petrova, N N; Kucher, E O

2012-01-01

The impact of treatment side-effects on the compliance was studied in 85 depressive patients with different mental disorders - recurrent depressive disorder, postschizophrenic depression and organic affective disorder. The comparison of objective and subjective evaluations of compliance and a comparative analysis of the level of compliance, with its dependence on the treatment specifics, in different diseases were done. A significant role of efficacy and treatment side-effects was identified. The levels of "mental" and "autonomous" side-effects were highest in the treatment of depression: patients with postschizophrenic depression had the highest risk in respect of maintenance treatment; patients with recurrent depressive disorder and organic (affective) disorder were more tolerant to the treatment side-effects and their treatment, including the maintenance therapy, was rather effective. The compliance of all patients with depression was negatively correlated with the severity of side-effects of pharmacotherapy. The greatest side-effects and the lowest level of compliance were observed in the complex treatment with antidepressants and atypical neuroleptics. The effect of side-effects on the compliance was dependent on their severity and subjective tolerability and, to a lesser extent, on the amount of drugs.

Transcranial Magnetic Stimulation: Basic Principles and Clinical Applications in Migraine.

PubMed

Barker, Anthony T; Shields, Kevin

2017-03-01

Transcranial magnetic stimulation (TMS) is a neurophysiological technique with a long established pedigree of safety, tolerability, and efficacy. Initially TMS was used to study the function of the cerebral cortex, but it has now become a treatment for migraine, one of the most common and debilitating neurological conditions. In this review we discuss the scientific background and development of the technique. We explore its application for the treatment of migraine and ponder the possible mechanisms of action in this most common neurological condition. The generation of brief magnetic pulses by a suitable coil can induce electrical fields in the body. When applied to the cerebral cortex, currents are painlessly induced in cortical neurons. These currents can lead to neuronal depolarization and may influence cortical excitability by means that are as yet not fully understood. This ability to modulate cortical excitability has been exploited as a treatment for migraine with aura. Aura is implicated in the pathophysiology of migraine. Experimental studies have shown that transcranial magnetic pulses can block waves of cortical spreading depression - the experimental equivalent of migrainous aura. Migraine is a debilitating condition characterized by headache, nausea, and sensory hypersensitivity. It may affect up to 15% of the population, yet current drug treatments are often poorly tolerated. Clinical studies have shown that TMS is an effective treatment for migraine. In addition, it has the added advantages of being safe and well tolerated by patients. © 2016 American Headache Society.

Five-level sub-axial cervical vertebrectomy and reconstruction: technical report.

PubMed

Reig, Adam; Parker, Scott L; McGirt, Matthew J

2014-05-01

Regardless of the etiology, severe cervical deformities can be extremely debilitating and are a challenge to correct. Often a multi-modality team approach is required to safely and effectively reduce the deformity, provide adequate decompression, and ensure solid fixation and fusion. In cases of iatrogenic cervical deformity necessitating five-level corpectomy and fixation, the feasibility, safety, and durability of this procedure remains unknown. We describe a patient who presented with debilitating pain and inability to eat due to an iatrogenic chin-on-chest cervical kyphotic deformity. The patient underwent a back-front-back staged procedure requiring five-level cervical vertebrectomy, C3-T1 anterior fixation, and occipital to T5 posterior fusion, resulting in successful reduction of cervical kyphosis from 75 to 0 degrees. At 6 months post-operatively, the patient demonstrated marked improvement in neurologic function and reported substantial improvements in neck pain-specific disability (NDI) and quality of life (SF-12 and EQ-5D). The feasibility and safety of five-level vertebrectomy and reconstruction for chin-on-chest deformity remains poorly described. The current case suggests that thoughtful planning that involves maximizing the patient's health status, judicious use of traction under direct neurological examination, staged circumferential release, and design of a construct that provides anterior and posterior column support with several points of fixation beyond the axis of rotation will attenuate the risk of peri-operative morbidity and potentiate the durability of deformity correction.

Exploring the associations between drug side-effects and therapeutic indications.

PubMed

Wang, Fei; Zhang, Ping; Cao, Nan; Hu, Jianying; Sorrentino, Robert

2014-10-01

Drug therapeutic indications and side-effects are both measurable patient phenotype changes in response to the treatment. Inferring potential drug therapeutic indications and identifying clinically interesting drug side-effects are both important and challenging tasks. Previous studies have utilized either chemical structures or protein targets to predict indications and side-effects. In this study, we compared drug therapeutic indication prediction using various information including chemical structures, protein targets and side-effects. We also compared drug side-effect prediction with various information sources including chemical structures, protein targets and therapeutic indication. Prediction performance based on 10-fold cross-validation demonstrates that drug side-effects and therapeutic indications are the most predictive information source for each other. In addition, we extracted 6706 statistically significant indication-side-effect associations from all known drug-disease and drug-side-effect relationships. We further developed a novel user interface that allows the user to interactively explore these associations in the form of a dynamic bipartitie graph. Many relationship pairs provide explicit repositioning hypotheses (e.g., drugs causing postural hypotension are potential candidates for hypertension) and clear adverse-reaction watch lists (e.g., drugs for heart failure possibly cause impotence). All data sets and highly correlated disease-side-effect relationships are available at http://astro.temple.edu/∼tua87106/druganalysis.html. Copyright © 2014 Elsevier Inc. All rights reserved.

Parental Expectation of Side Effects Following Vaccination Is Self-fulfilling: A Prospective Cohort Study.

PubMed

Smith, Louise E; Weinman, John; Amlôt, Richard; Yiend, Jenny; Rubin, G James

2018-06-02

One of the major factors contributing to parental refusal of vaccinations is the perception that vaccines cause side effects. Although symptoms are commonly reported following vaccinations, their causes are not always straightforward. Although some may be directly attributable to the vaccine itself, others may reflect pre-existing or coincidental symptoms that are misattributed to the vaccine. To investigate psychological factors associated with parental report of side effects following vaccination with the child influenza vaccine, and parental intention to re-vaccinate one's child the following year. A prospective cohort study was run in primary care practices in London in the 2016-2017 influenza season (ClinicalTrials.gov number NCT02909855). Two hundred seventy parents from 14 practices completed a questionnaire before their child's vaccination. Follow-up questionnaires were completed 3 days after vaccination and one month after vaccination. Parental report of side effects and vaccination intention for the subsequent year were measured. Parental report of side effects was strongly associated with pre-vaccination expectation of side effects. Suggestions received from the media, National Health Service (NHS) vaccination leaflet, and health care workers, as well as uncertainty-related beliefs, perceived sensitivity of the child to medicines, pessimism, and anxiety were also associated with reporting side effects. Side effect report was associated with lower vaccination intention for the following influenza season. Side effect perception following vaccination is influenced by psychological factors, in particular expectations. Perceiving side effects reduces future vaccination intention. Future public health communications should aim to decrease unrealistic expectations of side effects to increase vaccine uptake.

Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis

PubMed Central

Zielinski, Daniel C.; Filipp, Fabian V.; Bordbar, Aarash; Jensen, Kasper; Smith, Jeffrey W.; Herrgard, Markus J.; Mo, Monica L.; Palsson, Bernhard O.

2015-01-01

Drug side effects cause a significant clinical and economic burden. However, mechanisms of drug action underlying side effect pathogenesis remain largely unknown. Here, we integrate pharmacogenomic and clinical data with a human metabolic network and find that non-pharmacokinetic metabolic pathways dysregulated by drugs are linked to the development of side effects. We show such dysregulated metabolic pathways contain genes with sequence variants affecting side effect incidence, play established roles in pathophysiology, have significantly altered activity in corresponding diseases, are susceptible to metabolic inhibitors and are effective targets for therapeutic nutrient supplementation. Our results indicate that metabolic dysregulation represents a common mechanism underlying side effect pathogenesis that is distinct from the role of metabolism in drug clearance. We suggest that elucidating the relationships between the cellular response to drugs, genetic variation of patients and cell metabolism may help managing side effects by personalizing drug prescriptions and nutritional intervention strategies. PMID:26055627

Occupational Therapy for the Head and Neck Cancer Patient.

PubMed

Park, Priscilla; Hashmi, Mahjabeen

2018-01-01

Occupational therapy is a health profession concerned with promoting health and well-being through occupation. A diagnosis of head and neck cancer (HNC) often invokes fear and anxiety because of the potential negative impact of the diagnosis and/or treatment on lifestyle and well-being. Occupational therapists perform a unique and important role in addressing quality of life concerns for HNC patients through applied expertise in lifestyle management, facilitating the use of positive coping strategies and daily routine management. Occupational therapy concurrently assists HNC patients to effectively manage the debilitating stress and anxiety associated with HNC diagnosis, treatment, and recovery while facilitating a return to prior or adapted daily routines.

Hope and fatigue in chronic illness: The role of perceived stress.

PubMed

Hirsch, Jameson K; Sirois, Fuschia M

2016-04-01

Fatigue is a debilitating symptom of chronic illness that is deleteriously affected by perceived stress, a process particularly relevant to inflammatory disease. Hopefulness, a goal-based motivational construct, may beneficially influence stress and fatigue, yet little research has examined these associations. We assessed the relation between hope and fatigue, and the mediating effect of stress, in individuals with fibromyalgia, arthritis, and inflammatory bowel disease. Covarying age, sex, and pain, stress partially mediated the association between hope and fatigue; those with greater hope reported less stress and consequent fatigue. Therapeutically, bolstering hope may allow proactive management of stressors, resulting in less fatigue. © The Author(s) 2014.

Animal models of post-traumatic stress disorder: face validity

PubMed Central

Goswami, Sonal; Rodríguez-Sierra, Olga; Cascardi, Michele; Paré, Denis

2013-01-01

Post-traumatic stress disorder (PTSD) is a debilitating condition that develops in a proportion of individuals following a traumatic event. Despite recent advances, ethical limitations associated with human research impede progress in understanding PTSD. Fortunately, much effort has focused on developing animal models to help study the pathophysiology of PTSD. Here, we provide an overview of animal PTSD models where a variety of stressors (physical, psychosocial, or psychogenic) are used to examine the long-term effects of severe trauma. We emphasize models involving predator threat because they reproduce human individual differences in susceptibility to, and in the long-term consequences of, psychological trauma. PMID:23754973

Treatment of recalcitrant erosive oral lichen planus and desquamative gingivitis with oral apremilast.

PubMed

AbuHilal, Mohn'd; Walsh, Scott; Shear, Neil

2016-11-30

Erosive oral lichen planus and desquamative gingivitis are uncommon but severe debilitating variants of oral lichen planus. Treatment of these presentations is difficult and challenging. A 44-year-old woman was referred to the dermatology clinic with chronic painful lichen planus-related gingivitis and buccal erosions. She has failed multiple treatments including topical clobetasol and tacrolimus, intralesional corticosteroids and several systemic and immunosuppressive agents. Following completion of three months of treatment with oral apremilast at a dose of 30 mg twice daily, significant improvement was noted in her disease activity. Oral apremilast may be a safe and effective treatment for erosive oral lichen planus.

Eustrongylides and pesticide levels in a great blue heron shot in Wisconsin

USGS Publications Warehouse

Windingstad, R.M.; Swineford, D.M.

1981-01-01

The parasitic roundworm, Eustrongylides ignotus Jagersk, has been known to cause mortality and morbidity in members of the heron family in the eastern states of North America. To date no previous records exist for this nematode in Wisconsin. Even though eustrongylidiosis was first detected in the District of Columbia in 1926 by Chapin (1926), it was not until 1976 that this parasite was found in the midwest, in central Indiana (Winterfield and Kazacos 1977). The purpose of this report is to document the occurrence of this nematode even further westward in Wisconsin, and to show the debilitating effect it can have on herons.

Radiation Therapy Side Effects

Cancer.gov

Radiation therapy has side effects because it not only kills or slows the growth of cancer cells, it can also affect nearby healthy cells. Many people who get radiation therapy experience fatigue. Other side effects depend on the part of the body that is being treated. Learn more about possible side effects.

Influence of opioid-related side effects on disability, mood, and opioid misuse risk among patients with chronic pain in primary care.

PubMed

Jamison, Robert N; Dorado, Kathleen; Mei, Anna; Edwards, Robert R; Martel, Marc O

2017-03-01

There is increasing concern among primary care practitioners about the use of opioids for chronic pain, including their adverse effects, but little attention has been given to how reports of side effects from prescription medication can contribute to outcomes among patients with chronic pain. The aim of this study was to investigate the impact of frequently reported side effects on mood, disability, and opioid misuse in patients with chronic pain prescribed opioids within primary care. Two hundred (N = 200) patients with chronic pain taking opioids for pain were recruited into the study. All patients completed baseline measures and a monthly side effects checklist once a month for 6 months. Patients were divided evenly based on a median split of the number of endorsed side effects over 6 months. The subjects repeated the baseline measures at the end of the study period. Over time, reports of medication side effects tended to decrease, but differences in frequency of reported side effects from baseline to follow-up (6-month time) were not significant, and the order of the frequency of the reported side effects remained similar. Patients who reported significant medication-related adverse effects reported significantly greater activity interference, negative affect, and catastrophizing compared with those with fewer side effects ( P < 0.01). In addition, those patients with pain who reported more side effects showed significantly higher scores on opioid misuse risk ( P < 0.001). This study demonstrates the important role of monitoring medication-related side effects among patients with chronic pain who are prescribed opioid medication for pain within primary care.

Influence of opioid-related side effects on disability, mood, and opioid misuse risk among patients with chronic pain in primary care

PubMed Central

Jamison, Robert N.; Dorado, Kathleen; Mei, Anna; Edwards, Robert R.; Martel, Marc O.

2017-01-01

Abstract Background: There is increasing concern among primary care practitioners about the use of opioids for chronic pain, including their adverse effects, but little attention has been given to how reports of side effects from prescription medication can contribute to outcomes among patients with chronic pain. The aim of this study was to investigate the impact of frequently reported side effects on mood, disability, and opioid misuse in patients with chronic pain prescribed opioids within primary care. Methods: Two hundred (N = 200) patients with chronic pain taking opioids for pain were recruited into the study. All patients completed baseline measures and a monthly side effects checklist once a month for 6 months. Patients were divided evenly based on a median split of the number of endorsed side effects over 6 months. The subjects repeated the baseline measures at the end of the study period. Results: Over time, reports of medication side effects tended to decrease, but differences in frequency of reported side effects from baseline to follow-up (6-month time) were not significant, and the order of the frequency of the reported side effects remained similar. Patients who reported significant medication-related adverse effects reported significantly greater activity interference, negative affect, and catastrophizing compared with those with fewer side effects (P < 0.01). In addition, those patients with pain who reported more side effects showed significantly higher scores on opioid misuse risk (P < 0.001). Discussion: This study demonstrates the important role of monitoring medication-related side effects among patients with chronic pain who are prescribed opioid medication for pain within primary care. PMID:29392205

Side effects of low-dose pyridostigmine bromide are not related to cholinesterase inhibition.

PubMed

Cook, M R; Gerkovich, M M; Sastre, A; Graham, C

2001-12-01

Pretreatment with pyridostigmine bromide (PB) has become part of standard military procedures for protection against the effects of possible chemical warfare attack. The purpose of the work reported here was to quantify the type, intensity and frequency of side effects of low-dose PB, and to examine factors that predict the intensity and frequency of side effects. A double-blind, cross-over, placebo (PL)-controlled design was used. Of the 67 subjects, 33 received 30 mg PB every 8 h for 13 doses, and 34 received 60 mg on the same schedule. Order of PB and PL administration was counterbalanced. Overall, side effects were mild, even at the 60-mg dose level. More side effects were reported when volunteers were taking PB than when they were taking placebo. Women reported more symptoms than men. Neither cholinesterase inhibition nor plasma levels of PB predicted side effect scores during the PB week; the best predictor of side effect scores during the PB week was side effect scores during the PL week. PB is well tolerated by healthy young people, even when twice the recommended military dose is administered.

A Multimodal Approach in Dealing with Chronic Epstein-Barr Viral Syndrome.

ERIC Educational Resources Information Center

Weikel, William J.

1989-01-01

Discusses Epstein-Barr Viral Syndrome, a puzzling and controversial disease with a variety of symptoms that frequently include depression and emotional debilitation. Offers diagnostic signs and suggests a possible treatment strategy based on the multimodal approach. (Author/ABL)

Art Therapy for Chronic Pain: Applications and Future Directions

ERIC Educational Resources Information Center

Angheluta, Anne-Marie; Lee, Bonnie K.

2011-01-01

Chronic pain is acknowledged as a phenomenological experience resulting from biological, psychological, and social interactions. Consequently, treatment for this complex and debilitating health phenomenon is often approached from multidisciplinary and biopsychosocial perspectives. One approach to treating chronic pain involves implementing…

Stereotype threat and female communication styles.

PubMed

von Hippel, Courtney; Wiryakusuma, Cindy; Bowden, Jessica; Shochet, Megan

2011-10-01

A large body of research has documented the performance-debilitating effects of stereotype threat for individuals, but there is a paucity of research exploring interpersonal consequences of stereotype threat. Two experiments tested the hypothesis that stereotype threat would change the style in which women communicate. Results indicate that women who experience stereotype threat regarding leadership abilities react against the stereotype by adopting a more masculine communication style. Study 2 provides evidence that self-affirmation eliminates this effect of stereotype threat on women's communication styles. A third study demonstrates an ironic consequence of this effect of stereotype threat on women's communication--when women under stereotype threat adopt a more masculine communication style, they are rated as less warm and likeable, and evaluators indicate less willingness to comply with their requests. Theoretical and practical implications of these findings are discussed.

Effects of confidence and anxiety on flow state in competition.

PubMed

Koehn, Stefan

2013-01-01

Confidence and anxiety are important variables that underlie the experience of flow in sport. Specifically, research has indicated that confidence displays a positive relationship and anxiety a negative relationship with flow. The aim of this study was to assess potential direct and indirect effects of confidence and anxiety dimensions on flow state in tennis competition. A sample of 59 junior tennis players completed measures of Competitive State Anxiety Inventory-2d and Flow State Scale-2. Following predictive analysis, results showed significant positive correlations between confidence (intensity and direction) and anxiety symptoms (only directional perceptions) with flow state. Standard multiple regression analysis indicated confidence as the only significant predictor of flow. The results confirmed a protective function of confidence against debilitating anxiety interpretations, but there were no significant interaction effects between confidence and anxiety on flow state.

Designing Isoform-selective Inhibitors Against Classical HDACs for Effective Anticancer Therapy: Insight and Perspectives from In Silico.

PubMed

Ganai, Shabir Ahmad

2018-01-01

Histone deacetylase inhibitors, the small molecules modulating the biological activity of histone deacetylases are emerging as potent chemotherapeutic agents. Despite their considerable therapeutic benefits in disease models, the lack of isoform specificity culminates in debilitating off target effects, raising serious concerns regarding their applicability. This emphasizes the pressing and unmet medical need of designing isoform selective inhibitors for safe and effective anticancer therapy. Keeping these grim facts in view, the current article sheds light on structural basis of off-targeting. Furthermore, the article discusses extensively the role of in silico strategies such as Molecular Docking, Molecular Dynamics Simulation and Energetically-optimized structure based pharmacophore approach in designing on-target inhibitors against classical HDACs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Factors affecting patient's perception of anticancer treatments side-effects: an observational study.

PubMed

Russo, Stefania; Cinausero, Marika; Gerratana, Lorenzo; Bozza, Claudia; Iacono, Donatella; Driol, Pamela; Deroma, Laura; Sottile, Roberta; Fasola, Gianpiero; Puglisi, Fabio

2014-02-01

Analysis of relative importance of side effects of anticancer therapy is extremely useful in the process of clinical decision making. There is evidence that patients' perception of the side effects of anticancer treatments changes over time. Aim of this study was to evaluate the cancer patients' perceptions of physical and non-physical side effects of contemporary anticancer therapy. Four hundred and sixty-four patients entered the study (153 men and 311 women). Participants were asked to rank their side effects in order of distress by using two sets of cards naming physical and non-physical effects, respectively. Influencing factors, including treatment and patient characteristics, were also analysed. Patients ranked the non-physical side effect 'Affects my family or partner' first. 'Constantly tired' and 'Loss of hair' were ranked second and third, respectively. Significant differences from previous studies on this topic emerged. In particular, 'Vomiting', a predominant concern in previous studies, almost disappeared, whereas 'Nausea' and 'Loss of hair' remained important side effects in the patients' perception. Interestingly, marital status was predominant in driving patients' perception, being associated with several side effects ('Constantly tired', 'Loss of appetite', 'Affects my work/Home duties', 'Affects my social activities', 'Infertility'). Other significant factors influencing patient's perception of side effects included age, disease characteristics and ongoing anticancer therapy. This study provided information on current status of patients' perceptions of side effects of anticancer treatment. These results could be used in pre-treatment patient education and counselling.

Perceived risk of tamoxifen side effects: a study of the use of absolute frequencies or frequency bands, with or without verbal descriptors.

PubMed

Knapp, Peter; Gardner, Peter H; Raynor, David K; Woolf, Elizabeth; McMillan, Brian

2010-05-01

To investigate the effectiveness of presenting medicine side effect risk information in different forms, including that proposed by UK guidelines [[1] Medicines and Healthcare products Regulatory Agency. Always read the leaflet-Getting the best information with every medicine. (Report of the Committee on Safety of Medicines Working Group on Patient Information). London: The Stationery Office, 2005.]. 134 Cancer Research UK (CRUK) website users were recruited via a 'pop-up'. Using a 2x2 factorial design, participants were randomly allocated to one of four conditions and asked to: imagine they had to take tamoxifen, estimate the risks of 4 side effects, and indicate a presentation mode preference. Those presented with absolute frequencies demonstrated greater accuracy in estimating 2 of 4 side effects, and of any side effect occurring, than those presented with frequency bands. Those presented with combined descriptors were more accurate at estimating the risk of pulmonary embolism than those presented with numeric descriptors only. Absolute frequencies outperform frequency bands when presenting side effect risk information. However, presenting such exact frequencies for every side effect may be much less digestible than all side effects listed under 5 frequency bands. Combined numerical and verbal descriptors may be better than numeric only descriptors when describing infrequent side effects. Information about side effects should be presented in ways that patients prefer, and which result in most accurate risk estimates. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Preventive strategies for mental health.

PubMed

Arango, Celso; Díaz-Caneja, Covadonga M; McGorry, Patrick D; Rapoport, Judith; Sommer, Iris E; Vorstman, Jacob A; McDaid, David; Marín, Oscar; Serrano-Drozdowskyj, Elena; Freedman, Robert; Carpenter, William

2018-05-14

Available treatment methods have shown little effect on the burden associated with mental health disorders. We review promising universal, selective, and indicated preventive mental health strategies that might reduce the incidence of mental health disorders, or shift expected trajectories to less debilitating outcomes. Some of these interventions also seem to be cost-effective. In the transition to mental illness, the cumulative lifetime effect of multiple small effect size risk factors progressively increases vulnerability to mental health disorders. This process might inform different levels and stages of tailored interventions to lessen risk, or increase protective factors and resilience, especially during sensitive developmental periods. Gaps between knowledge, policy, and practice need to be bridged. Future steps should emphasise mental health promotion, and improvement of early detection and interventions in clinical settings, schools, and the community, with essential support from society and policy makers. Copyright © 2018 Elsevier Ltd. All rights reserved.

Laparoscopic bilateral transperitoneal adrenalectomy for Cushing syndrome: surgical challenges and lessons learnt.

PubMed

Aggarwal, Sandeep; Yadav, Kunal; Sharma, Aditya P; Sethi, Vrishketan

2013-06-01

Laparoscopic adrenalectomy is well established for treatment of adrenal lesions. However, bilateral adrenalectomy for Cushing syndrome is a challenging and time-consuming operation. We report our experience of laparoscopic bilateral adrenalectomy for this disease in 19 patients. From September 2009 to August 2012, we have operated 19 patients with Cushing syndrome and performed bilateral laparoscopic adrenalectomy using the transperitoneal approach; synchronous in 15 patients and staged in 4 patients. In 15 patients, the surgery was carried out sequentially on both the sides in lateral position with intraoperative change in position. Complete adrenalectomy including periadrenal fat was carried out on both the sides. Nineteen patients were referred from Department of Endocrinology for bilateral adrenalectomy for adrenocorticotropin hormone (ACTH)-dependent and ACTH-independent Cushing syndrome. The indications for surgery were Cushing disease in 15 patients, occult/ectopic source of ACTH in 2 patients, and primary adrenal hyperplasia in 2 patients. Fifteen patients underwent bilateral adrenalectomy during the same operation. Four patients underwent staged procedures. All procedures were completed laparoscopically with no conversions. The mean operating time for simultaneous bilateral adrenalectomy was 210 minutes (range, 150 to 240 min). This included the repositioning and reprepping time. There were no major intraoperative complications. The average blood loss was 100 mL (range, 50 to 200 mL). None of the patients required blood transfusions in the postoperative period. The postoperative complications included minor port-site infection in 2 patients. One severely debilitated patient died on the 14th postoperative day because of hospital-acquired pneumonia. The remaining 18 patients have done well in terms of impact on the disease. Laparoscopic bilateral adrenalectomy for Cushing syndrome is feasible and safe. It confers all the advantages of minimally invasive approach such as less postoperative pain, shorter hospitalization, lesser wound complications, and faster recovery. The advantages of the laparoscopic approach have led to an earlier referral for bilateral adrenalectomy by endocrinologist in patients with failed pituitary surgery.

Medication Side Effects among People with Epilepsy Taking Phenobarbital in Zambia

PubMed Central

Elafros, Melissa A.; Bui, Esther; Birbeck, Gretchen L.

2014-01-01

Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool Adverse Events Profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman’s correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1 mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4–8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the WHO report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects in routine care in low income settings is warranted. PMID:25219354

Medication side effects among people with epilepsy taking phenobarbital in Zambia.

PubMed

Elafros, Melissa A; Bui, Esther; Birbeck, Gretchen L

2014-11-01

Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool adverse events profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman's correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4-8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the World Health Organization report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects during routine care in low income settings is warranted. Copyright © 2014 Elsevier B.V. All rights reserved.

Reducing Aversion to Side Effects in Preventive Medical Treatment Decisions

ERIC Educational Resources Information Center

Waters, Erika A.; Weinstein, Neil D.; Colditz, Graham A.; Emmons, Karen M.

2007-01-01

Laypeople tend to be overly sensitive to side effects of treatments that prevent illness, possibly leading them to refuse beneficial therapies. This Internet-based study attempted to reduce such side effect aversion by adding graphic displays to the numerical risk probabilities. It also explored whether graphics reduce side effect aversion by…

Systematic identification of proteins that elicit drug side effects

PubMed Central

Kuhn, Michael; Al Banchaabouchi, Mumna; Campillos, Monica; Jensen, Lars Juhl; Gross, Cornelius; Gavin, Anne-Claude; Bork, Peer

2013-01-01

Side effect similarities of drugs have recently been employed to predict new drug targets, and networks of side effects and targets have been used to better understand the mechanism of action of drugs. Here, we report a large-scale analysis to systematically predict and characterize proteins that cause drug side effects. We integrated phenotypic data obtained during clinical trials with known drug–target relations to identify overrepresented protein–side effect combinations. Using independent data, we confirm that most of these overrepresentations point to proteins which, when perturbed, cause side effects. Of 1428 side effects studied, 732 were predicted to be predominantly caused by individual proteins, at least 137 of them backed by existing pharmacological or phenotypic data. We prove this concept in vivo by confirming our prediction that activation of the serotonin 7 receptor (HTR7) is responsible for hyperesthesia in mice, which, in turn, can be prevented by a drug that selectively inhibits HTR7. Taken together, we show that a large fraction of complex drug side effects are mediated by individual proteins and create a reference for such relations. PMID:23632385

Prediction of Central Nervous System Side Effects Through Drug Permeability to Blood-Brain Barrier and Recommendation Algorithm.

PubMed

Fan, Jun; Yang, Jing; Jiang, Zhenran

2018-04-01

Drug side effects are one of the public health concerns. Using powerful machine-learning methods to predict potential side effects before the drugs reach the clinical stages is of great importance to reduce time consumption and protect the security of patients. Recently, researchers have proved that the central nervous system (CNS) side effects of a drug are closely related to its permeability to the blood-brain barrier (BBB). Inspired by this, we proposed an extended neighborhood-based recommendation method to predict CNS side effects using drug permeability to the BBB and other known features of drug. To the best of our knowledge, this is the first attempt to predict CNS side effects considering drug permeability to the BBB. Computational experiments demonstrated that drug permeability to the BBB is an important factor in CNS side effects prediction. Moreover, we built an ensemble recommendation model and obtained higher AUC score (area under the receiver operating characteristic curve) and AUPR score (area under the precision-recall curve) on the data set of CNS side effects by integrating various features of drug.

An Ensemble Approach for Drug Side Effect Prediction

PubMed Central

Jahid, Md Jamiul; Ruan, Jianhua

2014-01-01

In silico prediction of drug side-effects in early stage of drug development is becoming more popular now days, which not only reduces the time for drug design but also reduces the drug development costs. In this article we propose an ensemble approach to predict drug side-effects of drug molecules based on their chemical structure. Our idea originates from the observation that similar drugs have similar side-effects. Based on this observation we design an ensemble approach that combine the results from different classification models where each model is generated by a different set of similar drugs. We applied our approach to 1385 side-effects in the SIDER database for 888 drugs. Results show that our approach outperformed previously published approaches and standard classifiers. Furthermore, we applied our method to a number of uncharacterized drug molecules in DrugBank database and predict their side-effect profiles for future usage. Results from various sources confirm that our method is able to predict the side-effects for uncharacterized drugs and more importantly able to predict rare side-effects which are often ignored by other approaches. The method described in this article can be useful to predict side-effects in drug design in an early stage to reduce experimental cost and time. PMID:25327524

The side-effects to CPAP treatment inventory: the development and initial validation of a new tool for the measurement of side-effects to CPAP treatment.

PubMed

Broström, Anders; Arestedt, Kristofer Franzén; Nilsen, Per; Strömberg, Anna; Ulander, Martin; Svanborg, Eva

2010-12-01

Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive sleep apnoea syndrome (OSAS), but side-effects are common. No validated self-rating scale measuring side-effects to CPAP treatment exists today. The aim was to develop the side-effects to CPAP treatment inventory (SECI), and investigate the validity and reliability of the instrument among patients with OSAS. SECI was developed on the basis of: (1) in-depth interviews with 23 patients; (2) examination of the scientific literature and (3) consensus agreement of a multi-professional expert panel. This yielded 15 different types of side-effects related to CPAP treatment. Each side-effect has three sub-questions (scales): perceived frequency (a) and magnitude (b) of the side-effect, as well as its perceived impact on CPAP use (c). A cross-sectional descriptive design was used. A total of 329 patients with OSAS with an average use of CPAP treatment for 39 months (2 weeks to 182 months) were recruited. Data were collected with SECI, and obtained from medical records (clinical variables and data related to CPAP treatment). Construct validity was confirmed with factor analysis (principal component analysis with orthogonal rotation). A logical two-factor solution, the device subscale and symptom subscale, emerged across all three scales. The symptom subscale describing physical and psychological side-effects and the device subscale described mask and device-related side-effects. Internal consistency reliability of the three scales was good (Cronbach's α = 0.74-0.86) and acceptable for the subscales (Cronbach's α = 0.62-0.86). The satisfactory measurement properties of this new instrument are promising and indicate that SECI can be used to measure side-effects to CPAP treatment. © 2010 European Sleep Research Society.

Community Colleges for International Development

ERIC Educational Resources Information Center

Hewitt, Martin J.; Lee, Ken

2006-01-01

Throughout the developing world, there is a debilitating lack of connection between tertiary education and economic growth. As a result, many tertiary institutions fail to address the particular human capital needs of the productive sector, thereby constraining economic growth, productivity and innovation. Existing employment opportunities go…

Acupuncture Reduces Breast Cancer Joint Pain | Division of Cancer Prevention

Cancer.gov

In the largest, most rigorous study of its kind, acupuncture was found to significantly reduce the debilitating joint pain experienced by tens of thousands of women each year while being treated for early stage breast cancer with aromatase inhibitors (AIs). |

77 FR 62267 - Proposed Extension of Existing Information Collection; Gamma Radiation Surveys

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-12

... Extension of Existing Information Collection; Gamma Radiation Surveys AGENCY: Mine Safety and Health...-9440 (voice); or 202-693-9441 (facsimile). SUPPLEMENTARY INFORMATION: I. Background Gamma radiation... debilitating occupational diseases. Natural sources include rocks, soils, and ground water. Gamma radiation...

Malnutrition: The Wasting of Human Potential.

ERIC Educational Resources Information Center

Taylor, Patricia S.

The paper discusses the prevalence of malnutrition in developing countries and the United States, particularly as it relates to debilitating physical and psychological disorders. Educational, social, and political factors which influence the cycle of malnutrition are described. Research on the relationship between malnutrition and intellectual…

Time to Talk: 5 Things To Know About Chronic Low-Back Pain and Complementary Health Practices

MedlinePlus

... even debilitating, and difficult to treat. Spinal manipulation, acupuncture, massage and yoga are complementary health approaches often ... and physical therapists. There is fair evidence that acupuncture is helpful in relieving chronic back pain. Current ...

Charcot Neuroarthropathy of the Foot and Ankle.

PubMed

Burson, Lisa K; Schank, Christopher H

2016-03-01

Charcot neuropathy is a painless, progressive, degeneration most notably of the ankle or midfoot joints, seen in patients with diabetes and neuropathy. This article will describe the etiology, diagnosis, and treatment of this potentially debilitating joint disease and provide implications for home care clinicians.

78 FR 26221 - National Mental Health Awareness Month, 2013

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-03

... conditions like depression and anxiety, post-traumatic stress and bipolar disorder--debilitating illnesses...-662-HELP. The National Suicide Prevention Lifeline offers immediate assistance for all Americans... depression screening and behavioral assessments for children at no extra cost to patients. My Administration...

Promoting Creative Tension within Collaborative Writing Groups.

ERIC Educational Resources Information Center

Ewald, Helen Rothschild; MacCallum, Virginia

1990-01-01

Describes a collaborative writing assignment which features a series of interconnected business messages arising out of a case study and including inhouse memos and an analytical report. Shows how the design of a collaborative writing assignment can foster creative rather than debilitative tension. (RS)

Relating drug–protein interaction network with drug side effects

PubMed Central

Mizutani, Sayaka; Pauwels, Edouard; Stoven, Véronique; Goto, Susumu; Yamanishi, Yoshihiro

2012-01-01

Motivation: Identifying the emergence and underlying mechanisms of drug side effects is a challenging task in the drug development process. This underscores the importance of system–wide approaches for linking different scales of drug actions; namely drug-protein interactions (molecular scale) and side effects (phenotypic scale) toward side effect prediction for uncharacterized drugs. Results: We performed a large-scale analysis to extract correlated sets of targeted proteins and side effects, based on the co-occurrence of drugs in protein-binding profiles and side effect profiles, using sparse canonical correlation analysis. The analysis of 658 drugs with the two profiles for 1368 proteins and 1339 side effects led to the extraction of 80 correlated sets. Enrichment analyses using KEGG and Gene Ontology showed that most of the correlated sets were significantly enriched with proteins that are involved in the same biological pathways, even if their molecular functions are different. This allowed for a biologically relevant interpretation regarding the relationship between drug–targeted proteins and side effects. The extracted side effects can be regarded as possible phenotypic outcomes by drugs targeting the proteins that appear in the same correlated set. The proposed method is expected to be useful for predicting potential side effects of new drug candidate compounds based on their protein-binding profiles. Supplementary information: Datasets and all results are available at http://web.kuicr.kyoto-u.ac.jp/supp/smizutan/target-effect/. Availability: Software is available at the above supplementary website. Contact: yamanishi@bioreg.kyushu-u.ac.jp, or goto@kuicr.kyoto-u.ac.jp PMID:22962476

Variations in judgments of intentional action and moral evaluation across eight cultures.

PubMed

Robbins, Erin; Shepard, Jason; Rochat, Philippe

2017-07-01

Individuals tend to judge bad side effects as more intentional than good side effects (the Knobe or side-effect effect). Here, we assessed how widespread these findings are by testing eleven adult cohorts of eight highly contrasted cultures on their attributions of intentional action as well as ratings of blame and praise. We found limited generalizability of the original side-effect effect, and even a reversal of the effect in two rural, traditional cultures (Samoa and Vanuatu) where participants were more likely to judge the good side effect as intentional. Three follow-up experiments indicate that this reversal of the side-effect effect is not due to semantics and may be linked to the perception of the status of the protagonist. These results highlight the importance of factoring cultural context in our understanding of moral cognition. Copyright © 2017. Published by Elsevier B.V.

Ischemia-Reperfusion Injury in Stroke

PubMed Central

Nour, May; Scalzo, Fabien; Liebeskind, David S.

2013-01-01

Despite ongoing advances in stroke imaging and treatment, ischemic and hemorrhagic stroke continue to debilitate patients with devastating outcomes at both the personal and societal levels. While the ultimate goal of therapy in ischemic stroke is geared towards restoration of blood flow, even when mitigation of initial tissue hypoxia is successful, exacerbation of tissue injury may occur in the form of cell death, or alternatively, hemorrhagic transformation of reperfused tissue. Animal models have extensively demonstrated the concept of reperfusion injury at the molecular and cellular levels, yet no study has quantified this effect in stroke patients. These preclinical models have also demonstrated the success of a wide array of neuroprotective strategies at lessening the deleterious effects of reperfusion injury. Serial multimodal imaging may provide a framework for developing therapies for reperfusion injury. PMID:25187778

Amiodarone-associated bilateral vestibulopathy.

PubMed

Gürkov, Robert; Manzari, Leonardo; Blödow, Alexander; Wenzel, Angela; Pavlovic, Dusan; Luis, Leonal

2018-03-01

Bilateral vestibulopathy (BVP) is a debilitating disorder characterized by the hypofunction of both vestibular end organs or nerves. The most frequent identifiable causes of BVP are ototoxic drug effects, infectious and autoimmune disorders. The majority of cases, however, remain idiopathic. Medical records of patients diagnosed with idiopathic BVP were examined in five dizziness clinics. We identified 126 patients with "idiopathic" BVP. Out of these, 15 patients had a history of Amiodarone treatment before the diagnosis of BVP, resulting in a 12% prevalence. The present report supports the hypothesis that Amiodarone can cause BVP. Vestibular examination in patients taking Amiodarone and suffering from balance-related symptoms are recommended, to recognize this adverse effect as early as possible and allow for an informed judgement on a potential dose reduction or withdrawal for recovery of the vestibular function.

Side-effects of topical steroids: A long overdue revisit.

PubMed

Coondoo, Arijit; Phiske, Meghana; Verma, Shyam; Lahiri, Koushik

2014-10-01

The introduction of topical steroids (TS) of varying potency have rendered the therapy of inflammatory cutaneous disorders more effective and less time-consuming. However the usefulness of these has become a double edged sword with constantly rising instances of abuse and misuse leading to serious local, systemic and psychological side effects. These side effects occur more with TS of higher potency and on particular areas of the body like face and genitalia. The article reviews the side effects of TS with special mention about peadiatric age group, also includes the measures for preventing the side effects.

Ultrasonic predator-prey interactions in water-convergent evolution with insects and bats in air?

PubMed

Wilson, Maria; Wahlberg, Magnus; Surlykke, Annemarie; Madsen, Peter Teglberg

2013-01-01

Toothed whales and bats have independently evolved biosonar systems to navigate and locate and catch prey. Such active sensing allows them to operate in darkness, but with the potential cost of warning prey by the emission of intense ultrasonic signals. At least six orders of nocturnal insects have independently evolved ears sensitive to ultrasound and exhibit evasive maneuvers when exposed to bat calls. Among aquatic prey on the other hand, the ability to detect and avoid ultrasound emitting predators seems to be limited to only one subfamily of Clupeidae: the Alosinae (shad and menhaden). These differences are likely rooted in the different physical properties of air and water where cuticular mechanoreceptors have been adapted to serve as ultrasound sensitive ears, whereas ultrasound detection in water have called for sensory cells mechanically connected to highly specialized gas volumes that can oscillate at high frequencies. In addition, there are most likely differences in the risk of predation between insects and fish from echolocating predators. The selection pressure among insects for evolving ultrasound sensitive ears is high, because essentially all nocturnal predation on flying insects stems from echolocating bats. In the interaction between toothed whales and their prey the selection pressure seems weaker, because toothed whales are by no means the only marine predators placing a selection pressure on their prey to evolve specific means to detect and avoid them. Toothed whales can generate extremely intense sound pressure levels, and it has been suggested that they may use these to debilitate prey. Recent experiments, however, show that neither fish with swim bladders, nor squid are debilitated by such signals. This strongly suggests that the production of high amplitude ultrasonic clicks serve the function of improving the detection range of the toothed whale biosonar system rather than debilitation of prey.

Insecticide residues in Australian plague locusts (Chortoicetes terminifera Walker) after ultra-low volume aerial application of the organophosphorus insecticide fenitrothion.

PubMed

Story, Paul G; Mineau, Pierre; Mullié, Wim C

2013-12-01

The need for locust control throughout eastern Australia during spring 2010 provided an opportunity to quantify residues of the organophosphorus insecticide fenitrothion on nymphs of the Australian plague locust, Chortoicetes terminifera Walker. Residues were collected across the different physiological states--live, dead, and debilitated (characterized by ease of capture, erratic hopping, and the inability to remain upright)--of locust nymphs observed following exposure to fenitrothion. The time course of residue depletion for 72 h after spraying was quantified, and residue-per-unit dose values in the present study were compared with previous research. Fenitrothion residue-per-unit dose values ranged from 0.2 µg/g to 31.2 µg/g (mean ± standard error [SE] = 6.3 ± 1.3 µg/g) in live C. terminifera nymps, from 0.5 µg/g to 25.5 µg/g (7.8 ± 1.3 µg/g) in debilitated nymphs, and from 2.3 µg/g to 39.8 µg/g (16.5 ± 2.8 µg/g) in dead nymphs. Residues of the oxidative derivative of fenitrothion, fenitrooxon, were generally below the limit of quantitation for the analysis (0.02 µg/g), with 2 exceptions--1 live and 1 debilitated sample returned residues at the limit of quantitation. The results of the present study suggest that sampling of acridids for risk assessment should include mimicking predatory behavior and be over a longer time course (preferably 3-24 h postspray) than sampling of vegetation (typically 1-2 h postspray) and that current regulatory frameworks may underestimate the risk of pesticides applied for locust or grasshopper control. © 2013 SETAC.

Effectiveness and side-effect profile of stimulant therapy as monotherapy and in combination in the central hypersomnias in clinical practice.

PubMed

Thakrar, Chiraag; Patel, Kishankumar; D'ancona, Grainne; Kent, Brian D; Nesbitt, Alexander; Selsick, Hugh; Steier, Joerg; Rosenzweig, Ivana; Williams, Adrian J; Leschziner, Guy D; Drakatos, Panagis

2017-10-19

Effectiveness and side-effect profile data on pharmacotherapy for daytime sleepiness in central hypersomnias are based largely upon randomized controlled trials. Evidence regarding the use of combination therapy is scant. The aim of this study was to examine the effectiveness and occurrence of drug-related side effects of these drugs in routine clinical practice. Adult patients diagnosed with a central hypersomnia during a 54-month period at a tertiary sleep disorders centre were identified retrospectively. Side effects were recorded at every follow-up visit. A total of 126 patients, with 3275 patient-months of drug exposure, were categorized into narcolepsy type 1 (n = 70), narcolepsy type 2 (n = 47) and idiopathic hypersomnia (n = 9). Modafinil was the most common drug used as a first-line treatment (93%) and in combination therapy (70%). Thirty-nine per cent of the patients demonstrated a complete, 25% partial and 36% a poor response to treatment. Combination treatment improved daytime sleepiness in 55% of the patients with residual symptoms despite monotherapy. Sixty per cent of patients reported side effects, and 30% reported treatment-limiting side effects. Drugs had similar side-effect incidence (P = 0.363) and their side-effect profile met those reported in the literature. Twenty-seven per cent of the patients received combination treatment and had fewer side effects compared to monotherapy (29.4% versus 60%, respectively, P = 0.001). Monotherapy appears to achieve satisfactory symptom control in most patients with central hypersomnia, but significant side effects are common. Combination therapy appears to be a useful and safe option in patients with refractory symptoms. © 2017 European Sleep Research Society.

Development of a data mining and imaging informatics display tool for a multiple sclerosis e-folder system

NASA Astrophysics Data System (ADS)

Liu, Margaret; Loo, Jerry; Ma, Kevin; Liu, Brent

2011-03-01

Multiple sclerosis (MS) is a debilitating autoimmune disease of the central nervous system that damages axonal pathways through inflammation and demyelination. In order to address the need for a centralized application to manage and study MS patients, the MS e-Folder - a web-based, disease-specific electronic medical record system - was developed. The e-Folder has a PHP and MySQL based graphical user interface (GUI) that can serve as both a tool for clinician decision support and a data mining tool for researchers. This web-based GUI gives the e-Folder a user friendly interface that can be securely accessed through the internet and requires minimal software installation on the client side. The e-Folder GUI displays and queries patient medical records--including demographic data, social history, past medical history, and past MS history. In addition, DICOM format imaging data, and computer aided detection (CAD) results from a lesion load algorithm are also displayed. The GUI interface is dynamic and allows manipulation of the DICOM images, such as zoom, pan, and scrolling, and the ability to rotate 3D images. Given the complexity of clinical management and the need to bolster research in MS, the MS e-Folder system will improve patient care and provide MS researchers with a function-rich patient data hub.

Reirradiation on recurrent cervical cancer case: Treatment response and side effects

NASA Astrophysics Data System (ADS)

Siregar, M. F.; Supriana, N.; Nuranna, L.; Prihartono, J.

2017-08-01

Management of recurrent cervical cancer by reirradiation after radiation treatment remains controversial. In Indonesia, there is currently no data about reirradiation tumor response and side effects. This study aims to assess the tumor response to and side effects of reirradiation, the effect of time interval between first radiation treatment and cancer recurrence on the tumor response and side effects, and the effect of tumor size on tumor response. A cohort retrospective study with no comparison was done with the Radiotherapy Department at Cipto Mangunkusumo General Hospital, Jakarta. Participants were recurrent cervical cancer patients undergoing reirradiation. Data was collected from patients’ medical records and follow-up phone calls. Twenty-two patients participated in this study. Nine patients (40.9%) had complete responses, 10 patients (45.5%) had partial responses, 1 patient (4.5%) had a stable response, and 2 patients (9.1%) had tumor progressions. In general, 15 patients (68.2%) had no to light side effects (grade 0-2 RTOG) and 7 patients (31.8%) had severe side effects (grade 3-4 RTOG). Four patients (18.1%) had severe gastrointestinal acute side effects, 6 patients (27.3%) had severe gastrointestinal late side effects, 2 patients (9.1%) had severe urogenital side effects, and there were no patients had severe urogenital late side effects. There was no significant difference in tumor response between patients with time interval between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was no significant difference in tumor response between patients with tumor size ≤4 cm vs. >4 cm. Reirradiation can be considered as a modality in recurrent cervical cancer management since good tumor response was achieved and the majority of patients had no to light side effects (grade 0-2 RTOG). This study found no correlation between tumor response, side effects, and time gap between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was also no correlation between tumor response and tumor size of ≤4 cm vs. > 4 cm.

Health care resource use and costs associated with possible side effects of high oral corticosteroid use in asthma: a claims-based analysis.

PubMed

Luskin, Allan T; Antonova, Evgeniya N; Broder, Michael S; Chang, Eunice Y; Omachi, Theodore A; Ledford, Dennis K

2016-01-01

The objective of this study was to estimate the prevalence of possible oral corticosteroid (OCS)-related side effects and health care resource use and costs in patients with asthma. This was a cross-sectional, matched-cohort, retrospective study using a commercial claims database. Adults with asthma diagnosis codes and evidence of asthma medication use were studied. Patients with high OCS use (≥30 days of OCS annually) were divided into those who did versus those who did not experience OCS-related possible side effects. Their health care resource use and costs were compared using linear regression or negative binomial regression models, adjusting for age, sex, geographic region, Charlson Comorbidity Index score, and chronic obstructive pulmonary disease status. After adjustment, high OCS users with possible side effects were more likely to have office visits (23.0 vs 19.6; P <0.001) and hospitalizations (0.44 vs 0.22; P <0.001) than those without possible side effects. Emergency department visits were similar between the groups. High OCS users with possible side effects had higher adjusted total annual mean health care costs ($25,168) than those without such side effects ($21,882; P =0.009). Among high OCS users, patients with possible OCS-related side effects are more likely to use health care services than those without such side effects. Although OCS may help control asthma and manage exacerbations, OCS side effects may result in additional health care resource use and costs, highlighting the need for OCS-sparing asthma therapies.

First Report of Protechinostoma mucronisertulatum (Echinostomatidae) in a Sandhill Crane (Grus canadensis) from Saskatchewan, Canada

USDA-ARS?s Scientific Manuscript database

We report a new host record for Protechinostoma mucronisertulatum. These small trematode parasites were found in a debilitated, immature, male sandhill crane (Grus canadensis) during Autumn migration from the Canadian prairies. Necropsy examination identified fibrinonecrotizing and ulcerative jejuni...

Managing Field Evacuations.

ERIC Educational Resources Information Center

Satz, Jay A.; McEvoy, David; Merrill, Kurt

In the event of a debilitating injury or illness, outdoor leaders should consider four critical phases in successfully managing backcountry field evaluations. The first phase, managing the immediate scene, involves assuring scene safety, medical care of the patient, instituting the emergency response plan, and providing for the needs of uninjured…

Retrospective Surveillance of Wastewater To Examine Seasonal Dynamics of Enterovirus Infections

EPA Science Inventory

Enteroviruses are RNA viruses that are responsible for both mild gastroenteritis and mild respiratory illnesses as well as debilitating diseases such as meningitis and myocarditis. The disease burden of enteroviruses in the United States is difficult to assess because most infect...

Reprioritization of Research for Combat Casualty Care

DTIC Science & Technology

2012-01-01

Today it is not un- common for a war casualty to sur- vive massive head trauma, multiple extremity loss, significant soft-tissue injury, and sensory ...disorder, depres- sion, and/or anxiety and the coexis- tence of debilitating pain syndromes, presents significant challenges to re- habilitation

ASTHMA AND MENTAL HEALTH SYMPTOMS AMONG ADULT ARAB AMERICANS IN THE DETROIT AREA

EPA Science Inventory

The burden of managing chronic health problems such as asthma is often compounded by psychological distress and debilitating mental health problems associated with these conditions. In this study we assessed the relationship between asthma and self-reported mental health symptom...

Macular Hole Development After Vitrectomy for Floaters: A Case Report.

PubMed

Appeltans, Andrea; Mura, Marco; Bamonte, Giulio

2017-12-01

The purpose of this report is to describe a case of macular hole development after vitrectomy for floaters with induction of posterior vitreous detachment. A 44-year-old otherwise healthy man presented with visually debilitating floaters in his right eye; these had been present for more than 2 years. Preoperative examination was unremarkable in both eyes, apart from some degree of vitreous degeneration in the right eye. Preoperative visual acuity was 20/20 bilaterally. A 25-gauge transconjunctival sutureless pars plana complete vitrectomy with induction of posterior vitreous detachment was performed in the right eye. Upon examination 1 month after surgery, a small full-thickness macular hole was detected in the right eye. Visual acuity was diminished to 20/80. The macular hole was closed after a second vitrectomy with internal limiting membrane peeling and gas tamponade. Macular hole development should be listed as a possible complication of vitrectomy for visually debilitating floaters when a posterior vitreous detachment is induced during surgery.

Does increased effort compensate for performance debilitating test anxiety?

PubMed

Putwain, David W; Symes, Wendy

2018-05-24

It is well established that test anxiety is negatively related to examination performance. Based on attentional control theory, the aim of this study was to examine whether increased effort can protect against performance debilitating test anxiety. Four hundred and sixty-six participants (male = 228; 48.9%; White = 346, 74.3%; mean age = 15.7 years) completed self-report measures of test anxiety and effort that were matched to performance on a high-stakes secondary school examination. The worry and bodily symptoms components of test anxiety were negatively, and effort, positively related to examination performance. Effort moderated the negative relation between bodily symptoms and examination performance. At low effort, the negative relationship was amplified and at high effort was attenuated. Compensatory effort protects performance against bodily symptoms but not worry. It is possible that the cognitive load on working memory arising from the combination of worry and examination demands may be too high to be compensated by effort. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Sleep Problems as Predictors in Attention-Deficit Hyperactivity Disorder: Causal Mechanisms, Consequences and Treatment.

PubMed

Um, Yoo Hyun; Hong, Seung-Chul; Jeong, Jong-Hyun

2017-02-28

Attention-deficit hyperactivity disorder (ADHD) is notorious for its debilitating consequences and early age of onset. The need for early diagnosis and intervention has frequently been underscored. Previous studies have attempted to clarify the bidirectional relationship between ADHD and sleep problems, proposing a potential role for sleep problems as early predictors of ADHD. Sleep deprivation, sleep-disordered breathing, and circadian rhythm disturbances have been extensively studied, yielding evidence with regard to their induction of ADHD-like symptoms. Genetic-phenotypic differences across individuals regarding the aforementioned sleep problems have been elucidated along with the possible use of these characteristics for early prediction of ADHD. The long-term consequences of sleep problems in individuals with ADHD include obesity, poor academic performance, and disrupted parent-child interactions. Early intervention has been proposed as an approach to preventing these debilitating outcomes of ADHD, with novel treatment approaches ranging from melatonin and light therapy to myofunctional therapy and adjustments of the time point at which school starts.

A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia.

PubMed

Dibonaventura, Marco; Gabriel, Susan; Dupclay, Leon; Gupta, Shaloo; Kim, Edward

2012-03-20

Antipsychotic medications often have a variety of side effects, however, it is not well understood how the presence of specific side effects correlate with adherence in a real-world setting. The aim of the current study was to examine the relationship between these variables among community-dwelling patients with schizophrenia. Data were analyzed from a 2007-2008 nationwide survey of adults who self-reported a diagnosis of schizophrenia and were currently using an antipsychotic medication (N = 876). The presence of side effects was defined as those in which the patient reported they were at least "somewhat bothered". Adherence was defined as a score of zero on the Morisky Medication Adherence Scale. To assess the relationship between side effects and adherence, individual logistic regression models were fitted for each side effect controlling for patient characteristics. A single logistic regression model assessed the relationship between side effect clusters and adherence. The relationships between adherence and health resource use were also examined. A majority of patients reported experiencing at least one side effect due to their medication (86.19%). Only 42.5% reported complete adherence. Most side effects were associated with a significantly reduced likelihood of adherence. When grouped as side effect clusters in a single model, extra pyramidal symptoms (EPS)/agitation (odds ratio (OR) = 0.57, p = 0.0007), sedation/cognition (OR = 0.70, p = 0.033), prolactin/endocrine (OR = 0.69, p = 0.0342), and metabolic side effects (OR = 0.64, p = 0.0079) were all significantly related with lower rates of adherence. Those who reported complete adherence to their medication were significantly less likely to report a hospitalization for a mental health reason (OR = 0.51, p = 0.0006), a hospitalization for a non-mental health reason (OR = 0.43, p = 0.0002), and an emergency room (ER) visit for a mental health reason (OR = 0.60, p = 0.008). Among patients with schizophrenia, medication side effects are highly prevalent and significantly associated with medication nonadherence. Nonadherence is significantly associated with increased healthcare resource use. Prevention, identification, and effective management of medication-induced side effects are important to maximize adherence and reduce health resource use in schizophrenia.

A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia

PubMed Central

2012-01-01

Background Antipsychotic medications often have a variety of side effects, however, it is not well understood how the presence of specific side effects correlate with adherence in a real-world setting. The aim of the current study was to examine the relationship between these variables among community-dwelling patients with schizophrenia. Methods Data were analyzed from a 2007-2008 nationwide survey of adults who self-reported a diagnosis of schizophrenia and were currently using an antipsychotic medication (N = 876). The presence of side effects was defined as those in which the patient reported they were at least "somewhat bothered". Adherence was defined as a score of zero on the Morisky Medication Adherence Scale. To assess the relationship between side effects and adherence, individual logistic regression models were fitted for each side effect controlling for patient characteristics. A single logistic regression model assessed the relationship between side effect clusters and adherence. The relationships between adherence and health resource use were also examined. Results A majority of patients reported experiencing at least one side effect due to their medication (86.19%). Only 42.5% reported complete adherence. Most side effects were associated with a significantly reduced likelihood of adherence. When grouped as side effect clusters in a single model, extra pyramidal symptoms (EPS)/agitation (odds ratio (OR) = 0.57, p = 0.0007), sedation/cognition (OR = 0.70, p = 0.033), prolactin/endocrine (OR = 0.69, p = 0.0342), and metabolic side effects (OR = 0.64, p = 0.0079) were all significantly related with lower rates of adherence. Those who reported complete adherence to their medication were significantly less likely to report a hospitalization for a mental health reason (OR = 0.51, p = 0.0006), a hospitalization for a non-mental health reason (OR = 0.43, p = 0.0002), and an emergency room (ER) visit for a mental health reason (OR = 0.60, p = 0.008). Conclusions Among patients with schizophrenia, medication side effects are highly prevalent and significantly associated with medication nonadherence. Nonadherence is significantly associated with increased healthcare resource use. Prevention, identification, and effective management of medication-induced side effects are important to maximize adherence and reduce health resource use in schizophrenia. PMID:22433036

Development of a New Self-Reporting Instrument Measuring Benefits and Side Effects of Corticosteroids in Duchenne Muscular Dystrophy: Report from a Pilot Study.

PubMed

Hendriksen, Ruben G F; Lionarons, Judith M; Hendriksen, Jos G M; Vles, Johan S H; McAdam, Laura C; Biggar, W Douglas

There is no cure for Duchenne Muscular Dystrophy (DMD); treatment is symptomatic and corticosteroids slow the progression. Side effects of corticosteroids - especially the physical effects - have been described, however patients' and caregivers perception on chronic corticosteroid treatment and their side effects is less well known, in particular with regards to cognition, behaviour, and emotional functioning. The primary aim of this pilot study was to (i) construct a self-report questionnaire to assess the perceived benefits and side effects of corticosteroids for patients with DMD and their parents. Furthermore we aimed to (ii) investigate the psychometric qualities of this questionnaire, (iii) whether there was a difference between parents' and patient's perceptions, and finally (iv) to what extent reported side effects may alter over time. A 23-item questionnaire (SIDECORT: side effect of corticosteroids) was constructed to assess the perception of these benefits and side effects in a systematic manner. In total, 86 patients (aged 5 - 28 years) and 125 of their parents completed the questionnaire. Internal consistency was good. Using factor analyses on the side effect items as reported by parents, two underlying factors were found, with the first factor describing cognitive, behavioural and emotional functioning, and the second factor describing physical functioning. The potential benefits of corticosteroids were highly rated among both parents and patients, although parents rated the importance of the benefits higher than their sons (p = 0.002). Similarly, parents rated the severity of the side effects generally higher than their sons (p = 0.011), especially with regards to the physical side effects (p = 0.014). Based on the parent's perception, the neurodevelopmental side effects generally appeared to decline the longer corticosteroids were used. To our knowledge, this is the first explicit study on perceived cognitive-, behavioural-, and emotional side effects and the allocation of benefits to corticosteroids in DMD. On the basis of our research we suggest a short form questionnaire, which proves to be reliable and valid for research- and clinical practice. This questionnaire could provide useful insights for the care of boys and men with DMD.

Central nervous system side effects associated with zolpidem treatment.

PubMed

Toner, L C; Tsambiras, B M; Catalano, G; Catalano, M C; Cooper, D S

2000-01-01

Zolpidem is one of the newer medications developed for the treatment of insomnia. It is an imidazopyridine agent that is an alternative to the typical sedative-hypnotic agents. Zolpidem use is gaining favor because of its efficacy and its side effect profile, which is milder and less problematic than that of the benzodiazepines and barbiturates used to treat insomnia. Still, side effects are not uncommon with zolpidem use. We report a series of cases in which the patients developed delirium, nightmares and hallucinations during treatment with zolpidem. We will review its pharmacology, discuss previous reports of central nervous system side effects, examine the impact of drug interactions with concurrent use of antidepressants, examine gender differences in susceptibility to side effects, and explore the significance of protein binding in producing side effects.

"Side effects affected my daily activities a lot": a qualitative exploration of the impact of contraceptive side effects in Bangladesh.

PubMed

Jain, Aparna; Reichenbach, Laura; Ehsan, Iqbal; Rob, Ubaidur

2017-01-01

In a country like Bangladesh that has made great progress in contraceptive use with one of the lowest levels of fertility and highest levels of contraceptive use, understanding what factors influence women's decisions to discontinue a contraceptive method and not switch to a new method is critical in designing interventions and programs that will help enable Bangladesh to reach its FP2020 goals. Research on side effects has focused on physical manifestations like headaches, moodiness, abdominal pain, and menstrual irregularities. While physical effects alone may stop women from continuing a contraceptive method, less is known about how side effects influence women's daily activities and lives. The purpose of this study is to understand the ways that side effects affect Bangladeshi women's participation in different social settings. Thirty-five in-depth interviews with married women who recently discontinued or switched to a different contraceptive method were conducted in Sylhet and Khulna Divisions. Interviews explored reasons for discontinuation including experience of side effects and impact of side effects on women's lives. Key themes emerged including that side effects are not only experienced physically but are barriers to women's participation in many aspects of their lives. The spheres of life that most commonly appeared to be influenced by side effects include religion, household, and sexual intimacy irrespective of method used or residence. Family planning providers need to be aware of these additional consequences associated with contraceptive side effects to provide tailored counseling that recognizes these issues and helps women to mitigate them. For Bangladesh to achieve its FP2020 goals, understanding the broader context in which family planning decisions are made vis-à-vis side effects is critical to design programs and interventions that meet all the needs of women beyond just their fertility intentions.

Side Effects (Management)

MedlinePlus

... cancer care is relieving side effects, called symptom management, palliative care, or supportive care. It is important ... treat them. To learn about the symptoms and management of the long-term side effects of cancer ...

What side effects are problematic for patients prescribed antipsychotic medication? The Maudsley Side Effects (MSE) measure for antipsychotic medication.

PubMed

Wykes, T; Evans, J; Paton, C; Barnes, T R E; Taylor, D; Bentall, R; Dalton, B; Ruffell, T; Rose, D; Vitoratou, S

2017-10-01

Capturing service users' perspectives can highlight additional and different concerns to those of clinicians, but there are no up to date, self-report psychometrically sound measures of side effects of antipsychotic medications. Aim To develop a psychometrically sound measure to identify antipsychotic side effects important to service users, the Maudsley Side Effects (MSE) measure. An initial item bank was subjected to a Delphi exercise (n = 9) with psychiatrists and pharmacists, followed by service user focus groups and expert panels (n = 15) to determine item relevance and language. Feasibility and comprehensive psychometric properties were established in two samples (N43 and N50). We investigated whether we could predict the three most important side effects for individuals from their frequency, severity and life impact. MSE is a 53-item measure with good reliability and validity. Poorer mental and physical health, but not psychotic symptoms, was related to side-effect burden. Seventy-nine percent of items were chosen as one of the three most important effects. Severity, impact and distress only predicted 'putting on weight' which was more distressing, more severe and had more life impact in those for whom it was most important. MSE is a self-report questionnaire that identifies reliably the side-effect burden as experienced by patients. Identifying key side effects important to patients can act as a starting point for joint decision making on the type and the dose of medication.

Managing Chemotherapy Side Effects: Constipation

MedlinePlus

... ational C ancer I nstitute Managing Chemotherapy Side Effects Constipation Take these steps: Eat high-fiber foods ... SERVICES National Institutes of Health Managing Chemotherapy Side Effects: Constipation These foods may help if you are ...

HIV Medicines and Side Effects

MedlinePlus

... Apps skip to content Side Effects of HIV Medicines Home Understanding HIV/AIDS Fact Sheets HIV Medicines ... p.m. ET) Send us an email HIV Medicines and Side Effects Last Reviewed: October 9, 2017 ...

Probiotics: Safety and Side Effects

MedlinePlus

... of this page please turn JavaScript on. Feature: Probiotics Safety and Side Effects Past Issues / Winter 2016 ... Says About the Safety and Side Effects of Probiotics Whether probiotics are likely to be safe for ...

Managing Chemotherapy Side Effects: Pain

MedlinePlus

N ational C ancer I nstitute Managing Chemotherapy Side Effects Pain It’s important to treat pain. If ... help to pay for pain medicine. Managing Chemotherapy Side Effects: Pain Keep track of the pain. Each ...

Managing Chemotherapy Side Effects: Memory Changes

MedlinePlus

... C ancer I nstitute Managing Chemotherapy Side Effects Memory Changes What is causing these changes? Your doctor ... thinking or remembering things Managing Chemotherapy Side Effects: Memory Changes Get help to remember things. Write down ...

Giant scrotal elephantiasis.

PubMed

Kuepper, Daniel

2005-02-01

How much can a man carry? Penoscrotal elephantiasis is a debilitating syndrome. This is a case report of a patient with giant genital elephantiasis secondary to long-standing lymphogranuloma venereum infection in Ethiopia. Complete surgical resection of the pathologic tissue and penile reconstruction was undertaken with good cosmetic and functional results.

Physical Assault of School Personnel

ERIC Educational Resources Information Center

Kajs, Lawrence T.; Schumacher, Gary; Vital, Cheryl A.

2014-01-01

Physical assault against school personnel is a serious problem, although not highly publicized. This workplace violence can result in debilitating injury to school employees along with major monetary costs. This article looks at legal issues that address physical assault against school personnel as well as the roles professional associations have…

Reward Processing in Adolescents with Bipolar I Disorder

ERIC Educational Resources Information Center

Singh, Manpreet K.; Chang, Kiki D.; Kelley, Ryan G.; Cui, Xu; Sherdell, Lindsey; Howe, Meghan E.; Gotlib, Ian H.; Reiss, Allan L.

2013-01-01

Objective: Bipolar disorder (BD) is a debilitating psychiatric condition that commonly begins in adolescence, a developmental period that has been associated with increased reward seeking. Because youth with BD are especially vulnerable to negative risk-taking behaviors, understanding the neural mechanisms by which dysregulated affect interacts…

Investing in the Future World Order: Geoeconomic Strategy and Foreign Direct Investment

DTIC Science & Technology

2017-06-01

systems and assets would have debilitating impact on security, national economic security, national public health or safety , or any combination of... Malaysia came to a similar agreement with China in order to resolve their dispute. Rather than relying on Western-established institutions, both

Putative rust fungal effector proteins in infected bean and soybean leaves

USDA-ARS?s Scientific Manuscript database

The plant pathogenic fungi Uromyces appendiculatus and Phakopsora pachyrhizi cause debilitating rust diseases on common bean and soybean. These rust fungi secrete effector proteins that allow them to infect plants, but the effector repertoire for U. appendiculatus and P. pachyrhizi is not fully def...

Teacher Identification of Student Learned Helplessness in Mathematics

ERIC Educational Resources Information Center

Yates, Shirley

2009-01-01

Teachers frequently encounter students with learned helplessness who are discouraged, turned off, or have given up trying to learn mathematics. Although learned helplessness has a long history in psychology, there has been no reliable means by which mathematics teachers can identify students exhibiting these debilitating yet changeable…

Voice Therapy Techniques Adapted to Treatment of Habit Cough: A Pilot Study.

ERIC Educational Resources Information Center

Blager, Florence B.; And Others

1988-01-01

Individuals with long-standing habit cough having no organic basis can be successfully treated with a combination of psychotherapy and speech therapy. Techniques for speech therapy are adapted from those used with hyperfunctional voice disorders to fit this debilitating laryngeal disorder. (Author)

21 CFR 522.1244 - Levamisole phosphate injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Levamisole phosphate injection. 522.1244 Section 522.1244 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... your veterinarian before using in severely debilitated animals or animals under severe stress. Do not...

The pathogen-occupied vacuoles of anaplasma phagocytophilum and anaplasma marginale interact with the endoplasmic reticulum

USDA-ARS?s Scientific Manuscript database

The genus Anaplasma consists of tick-transmitted obligate intracellular bacteria that invade white or red blood cells to cause debilitating and potentially fatal infections. A. phagocytophilum, a human and veterinary pathogen, infects neutrophils to cause granulocytic anaplasmosis. A. marginale inva...

Zinc and Diarrheal Disease - Control Status and Future Perspectives

USDA-ARS?s Scientific Manuscript database

Diarrhea is a public health problem world-wide. Although elimination of exposure to infectious pathogens is the primary means to combat this debilitating malady, use of oral zinc supplementation has been used to prevent and treat acute diarrhea in children. Evidence suggests that supplemental zinc...

Learned Helplessness: Theory and Evidence

ERIC Educational Resources Information Center

Maier, Steven F.; Seligman, Martin E. P.

1976-01-01

Authors believes that three phenomena are all instances of "learned helplessness," instances in which an organism has learned that outcomes are uncontrollable by his responses and is seriously debilitated by this knowledge. This article explores the evidence for the phenomena of learned helplessness, and discussed a variety of theoretical…

The Influence of Social Modeling, Gender, and Empathy on Treatment Side Effects.

PubMed

Faasse, Kate; Parkes, Bryony; Kearney, James; Petrie, Keith J

2018-05-31

Social modeling has the capacity to shape treatment outcomes, including side effects. This study investigated the influence of social modeling of treatment side effects, gender, and participant empathy, on side effects of a placebo treatment. Ninety-six participants (48 females) completed a study purportedly investigating the influence of modafinil (actually placebo) on alertness and fatigue. The participants were randomly seated with a male or female confederate and saw this confederate report experiencing side effects or no side effects. Participant empathy was assessed at baseline. Changes in modeled and general symptoms, and misattribution of symptoms, were assessed during the session and at 24-hr follow-up. During the experimental session, seeing side effect modeling significantly increased modeled symptoms (p = .023, d = 0.56) but not general or misattributed symptoms. Regardless of modeling condition, female participants seated with a female model reported significantly more general symptoms during the session. However, response to social modeling did not differ significantly by model or participant gender. At follow-up, the effect of social modeling of side effects had generalized to other symptoms, resulting in significantly higher rates of modeled symptoms (p = .023, d = 0.48), general symptoms (p = .013, d = 0.49), and misattributed symptoms (p = .022, d = 0.50). The experience of modeled symptoms in response to social modeling was predicted by participants' levels of baseline empathy. Social modeling of symptoms can increase the side effects following treatment, and this effect appears to generalize to a broader range of symptoms and symptom misattribution over time. Higher baseline empathy seems to increase response to social modeling.

"Side effects" of ECT are mainly depressive phenomena and are independent of age.

PubMed

Brodaty, H; Berle, D; Hickie, I; Mason, C

2001-10-01

The aetiology of reported side effects of electroconvulsive therapy (ECT) is unclear. We examined the interaction of depression and age on adverse neuropsychological and putative side effects of ECT. Inpatients (N=81; median age 70 years) with major depression were assessed prospectively pre-ECT, immediately post-ECT and 1-3 years later. Patients were administered the Hamilton Rating Scale for Depression (HRSD), the Global Assessment of Functioning scale (GAF) and neuropsychological tests from the Wechsler Memory Scale. Side effects and total burden scores were rated pre- and post-treatment. HRSD and GAF scores improved with treatment after ECT, but the prevalence and total burden of side effects were unchanged. Side effect burden was related to depression level before and after ECT. Improvement in depression correlated with reduction in side effect burden. There was a significant decline in side effect burden after controlling for change in depression. Patients' scores on neuropsychological measures did not appear to change after ECT or between pre-ECT and follow-up. Re-analysis, allowing for age, chronicity of depression, medication use and development of dementia, did not alter the findings. lack of a control group, lack of information on ECT technique, incomplete data sets and limited neuropsychological testing. ECT, an effective treatment for depression, does not cause significant side effects or neuropsychological impairment, which are more likely to be depressive phenomena. ECT appears to be safe for old (> or =65 years) and very old (> or =75 years) patients, who do not appear to be more susceptible to adverse effects.

A hierarchical anatomical classification schema for prediction of phenotypic side effects

PubMed Central

Kanji, Rakesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a ‘hierarchical anatomical classification schema’ which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects. PMID:29494708

A hierarchical anatomical classification schema for prediction of phenotypic side effects.

PubMed

Wadhwa, Somin; Gupta, Aishwarya; Dokania, Shubham; Kanji, Rakesh; Bagler, Ganesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a 'hierarchical anatomical classification schema' which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects.

Neuro-linguistic programming and application in treatment of phobias.

PubMed

Karunaratne, Mahishika

2010-11-01

Phobias are a prevalent and often debilitating mental health problem all over the world. This article aims to explore what is known about the use of Neuro-linguistic Programming (NLP) as a treatment for this condition. Whilst there is abundant experiential evidence from NLP practitioners attesting to the efficacy of this method as a treatment for phobias, experimental research in this area is somewhat limited. This paper reviews evidence available in literature produced in the UK and US and reveals that NLP is a successful treatment for phobias as well as being particularly efficient due to the relatively brief time period it takes to effect an improvement. Copyright © 2010 Elsevier Ltd. All rights reserved.

Quantitative MR assessment of longitudinal parenchymal changes in children treated for medulloblastoma

NASA Astrophysics Data System (ADS)

Reddick, Wilburn E.; Glass, John O.; Wu, Shingjie; Palmer, Shawna L.; Mulhern, Raymond K.; Gajjar, Amar

2002-05-01

Our research builds on the hypothesis that white matter damage, in children treated for cancer with cranial spinal irradiation, spans a continuum of severity that can be reliably probed using non-invasive MR technology and results in potentially debilitating neurological and neuropsychological problems. This longitudinal project focuses on 341 quantitative volumetric MR examinations from 58 children treated for medulloblastoma (MB) with cranial irradiation (CRT) of 35-40 Gy. Quadratic mixed effects models were used to fit changes in tissue volumes (white matter, gray matter, CSF, and cerebral) with time since CRT and age at CRT as covariates. We successfully defined algorithms that are useful in the prediction of brain development among children treated for MB.

A complex adenovirus vaccine against chikungunya virus provides complete protection against viraemia and arthritis

PubMed Central

Wang, Danher; Suhrbier, Andreas; Penn-Nicholson, Adam; Woraratanadharm, Jan; Gardner, Joy; Luo, Min; Le, Thuy T.; Anraku, Itaru; Sakalian, Michael; Einfeld, David; Dong, John Y.

2011-01-01

Chikungunya virus, a mosquito-borne alphavirus, recently caused the largest epidemic ever seen for this virus. Chikungunya disease primarily manifests as a painful and debilitating arthralgia/arthritis, and no effective drug or vaccine is currently available. Here we describe a recombinant chikungunya virus vaccine comprising a non-replicating complex adenovirus vector encoding the structural polyprotein cassette of chikungunya virus. A single immunisation with this vaccine consistently induced high titres of anti-chikungunya virus antibodies that neutralised both an old Asian isolate and a Réunion Island isolate from the recent epidemic. The vaccine also completely protected mice against viraemia and arthritic disease caused by both virus isolates. PMID:21320541

The influence of iron deficiency on the functioning of skeletal muscles: experimental evidence and clinical implications.

PubMed

Stugiewicz, Magdalena; Tkaczyszyn, Michał; Kasztura, Monika; Banasiak, Waldemar; Ponikowski, Piotr; Jankowska, Ewa A

2016-07-01

Skeletal and respiratory myopathy not only constitutes an important pathophysiological feature of heart failure and chronic obstructive pulmonary disease, but also contributes to debilitating symptomatology and predicts worse outcomes in these patients. Accumulated evidence from laboratory experiments, animal models, and interventional studies in sports medicine suggests that undisturbed systemic iron homeostasis significantly contributes to the effective functioning of skeletal muscles. In this review, we discuss the role of iron status for the functioning of skeletal muscle tissue, and highlight iron deficiency as an emerging therapeutic target in chronic diseases accompanied by a marked muscle dysfunction. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

An Examination of Psychotropic Medication Side Effects: Does Taking a Greater Number of Psychotropic Medications from Different Classes Affect Presentation of Side Effects in adults with ID?

ERIC Educational Resources Information Center

Mahan, Sara; Holloway, Jodie; Bamburg, Jay W.; Hess, Julie A.; Fodstad, Jill C.; Matson, Johnny L.

2010-01-01

This study examined whether the number of psychotropic medications an individual is taking across classes influences side effects among adults with Intellectual Disability (ID). Participants were 80 adults diagnosed with ID. Dependent variables were the composite score and domain scores of the "Matson Evaluation of Drug Side-Effects" ("MEDS"),…

Managing Chemotherapy Side Effects: Anemia

MedlinePlus

... ational C ancer I nstitute Managing Chemotherapy Side Effects Anemia “I told my doctor that I was ... exercise a little every day. Managing Chemotherapy Side Effects: Anemia Eat and drink well. ● ● Talk with your ...

Chemotherapy Side Effects: A Cause of Heart Disease?

MedlinePlus

... Can chemotherapy side effects increase the risk of heart disease? Answers from Timothy J. Moynihan, M.D. Chemotherapy side effects may increase the risk of heart disease, including weakening of the heart muscle (cardiomyopathy) and ...

Managing Chemotherapy Side Effects: Skin and Nail Changes

MedlinePlus

... ational C ancer I nstitute Managing Chemotherapy Side Effects Skin and Nail Changes “I was glad to ... services national institutes of health Managing Chemotherapy Side Effects: Skin and Nail Changes Protect your skin from ...

Cutaneous side effects of doxycycline: a pediatric case series.

PubMed

Bayhan, Gulsum Iclal; Akbayram, Sinan; Ozaydin Yavuz, Goknur; Oner, Ahmet Fayik

2017-06-01

Brucellosis is highly endemic in Turkey and doxycycline is commonly used for its treatment. The present study aimed at documenting the cutaneous side effects of doxycycline in pediatric brucellosis patients in Turkey. Pediatric patients with brucellosis that were treated between February 2014 and January 2016 were analyzed retrospectively, and those that developed doxycycline-related cutaneous side effects were identified. Demographic data, epidemiological history, physical examination findings, laboratory test results, anti-brucellosis treatment regimen, duration of follow up and outcome were recorded. Among the 189 brucellosis patients, 141 treated with doxycycline plus rifampicin. Seven patients (5%) (two female and five male) developed doxycycline-related cutaneous side effects. Mean duration of treatment before the onset of cutaneous side effects was 9.5 weeks. Doxycycline therapy was continued in five of these patients and was changed in two patients. In the patients that continued to receive doxycycline the cutaneous side effects gradually improved. Cutaneous side effects of doxycycline should always be a consideration, especially in regions in which brucellosis is endemic and doxycycline is commonly used to treat it.

Influence of Side Effects on ART Adherence Among PLWH in China: The Moderator Role of ART-Related Knowledge.

PubMed

Zhou, Guangyu; Li, Xiaoming; Qiao, Shan; Shen, Zhiyong; Zhou, Yuejiao

2018-03-01

Despite the medical advancements in HIV treatment, realities of side effects are faced by people living with HIV (PLWH) who receive antiretroviral therapy (ART). Mixed findings have been reported on the association between side effects and ART adherence. However, few studies have explored the combined side effects and behavior-related information on medication adherence. The aim of the current study is to examine moderator role of ART-related knowledge between side effects and ART adherence. A cross-sectional survey was conducted among 2987 PLWH from October 2012 to August 2013 in China. Of the total sample, 2095 patients had received ART and provided ART adherence. Side effects, ART-related knowledge, and ART adherence, as well as potential covariates were assessed. The results revealed that there was a negative relationship of side effects and ART adherence existed among low and medium levels of ART-related knowledge, but not among high level of knowledge. Future interventions to promote HIV medication adherence should focus on providing behavior-related information education among PLWH.

Cancer Treatment Side Effects: A Meta-analysis of the Relationship Between Response Expectancies and Experience.

PubMed

Devlin, Elise J; Denson, Linley A; Whitford, Hayley S

2017-08-01

Although previous research has, overall, suggested a moderate relationship between response expectancies (REs) and cancer treatment-related side effects, empirical results have been mixed. We aimed to further explore these relationships, hypothesizing that REs would predict subsequent toxicities with the inclusion of more recent studies, across a broader range of side effects, while incorporating the impact of potential moderators including patients' experience with treatment and measurement methods. We further investigated the impact of REs across individual toxicities. A systematic search and analysis were conducted across four databases (PsychInfo, PubMed, CINAHL, and Embase) and reference lists, from 1985 to February 2016. This provided 27 eligible studies with 4474 participants, through which the main analysis, moderator analyses, and individual side-effect analyses were explored. REs were moderately related to side effects overall (r = 0.26), and effect sizes were significantly influenced by sample diagnostic homogeneity, whereas differences between type and timing of measurement showed trends. Of the 16 toxicities examined, 15 demonstrated significant relationships between REs and side-effect experience, with hair loss (r = 0.48) the strongest. No clear difference emerged between objective and subjective side effects; however, significant differences across individual toxicities were revealed. Findings support a relationship between REs and a wide range of subsequent side effects, yet differences between individual RE-toxicity associations emerged. These findings provide direction for the measurement of side effects and REs and support REs as potential targets for intervention during the informed consent process. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Anaesthesiological considerations on tocolytic and uterotonic therapy in obstetrics.

PubMed

Vercauteren, M; Palit, S; Soetens, F; Jacquemyn, Y; Alahuhta, S

2009-07-01

Significant side effects of tocolytic and uterotonic substances may be of concern to the anaesthesiologist. Recently, new drugs have been introduced having less side effects for both the mother and the neonate. A literature search was undertaken mainly focusing on meta-analyses, to review the possible side effects that might affect the course of anaesthesia and to suggest which precautions should be considered to prevent the occurrence of significant interactions with anaesthetic manipulations and drugs. Magnesium sulphate has a proven benefit in lowering systolic blood pressure and preventing the occurrence of eclampsia, but not as a tocolytic. beta-adrenergic agonists are being abandoned due to the availability of tocolytic agents causing less side effects. Calcium channel blockers (CCB) are frequently used but can cause major maternal cardiovascular complications. Nitroglycerin seems to be appreciated as an acute tocolytic rather than a routine substance during pre-term labour. Cyclo-oxygenase-2 inhibitors are still under investigation but their tocolytic benefit is questionable mainly due to foetal side effects. Atosiban is considered the first-choice tocolytic. With respect to oxytocic drugs, oxytocine, prostaglandines and methylergometrine may all cause serious side effects especially when combined. The cardiovascular side effects of prostaglandins and methylergometrine can be life-threatening. Both oxytocin and carbetocin have a rather low risk for maternal complications. Atosiban and CCB are at least as effective tocolytic agents as beta-mimetics but have significantly less side effects. Magnesium sulphate can cause neuromuscular blockade, especially when combined with CCB. Concerning oxytocic agents, short-acting oxyctocin and long-acting carbetocin have the least side effects as compared with prostaglandins and methylergometrine.

Male-female differences in the effects of cannabinoids on sexual behavior and gonadal hormone function.

PubMed

Gorzalka, Boris B; Hill, Matthew N; Chang, Sabrina C H

2010-06-01

The putative role of the endocannabinoid system and the effects of cannabis use in male and female sexual functioning are summarized. The influence of cannabis intake on sexual behavior and arousability appear to be dose-dependent in both men and women, although women are far more consistent in reporting facilitatory effects. Furthermore, evidence from nonhuman species indicate somewhat more beneficial than debilitating effects of cannabinoids on female sexual proceptivity and receptivity while suggesting predominantly detrimental effects on male sexual motivation and erectile functioning. Data from human and nonhuman species converge on the ephemeral nature of THC-induced testosterone decline. However, it is clear that cannabinoid-induced inhibition of male sexual behavior is independent of concurrent declines in testosterone levels. Investigations also reveal a suppression of gonadotropin release by cannabinoids across various species. Historical milestones and promising future directions in the area of cannabinoid and sexuality research are also outlined in this review. Copyright 2009 Elsevier Inc. All rights reserved.

A single dose of lysergic acid diethylamide influences gene expression patterns within the mammalian brain.

PubMed

Nichols, Charles D; Sanders-Bush, Elaine

2002-05-01

Hallucinogenic drugs such as lysergic acid diethylamide (LSD) have profound effects on humans including hallucinations and detachment from reality. These remarkable behavioral effects have many similarities to the debilitating symptoms of neuropsychiatric disorders such as schizophrenia. The effects of hallucinogens are thought to be mediated by serotonin receptor activation; however, how these drugs elicit the unusual behavioral effects remains largely a mystery, despite much research. We have undertaken the first comprehensive analysis of gene expression influenced by acute LSD administration in the mammalian brain. These studies represent a novel approach to elucidate the mechanism of action of this class of drugs. We have identified a number of genes that are predicted to be involved in the processes of synaptic plasticity, glutamatergic signaling and cytoskeletal architecture. Understanding these molecular events will lead to new insights into the etiology of disorders whose behavioral symptoms resemble the temporary effects of hallucinogenic drugs, and also may ultimately result in new therapies.

Type and frequency of side effects during PC6 acupuncture: observations from therapists and patients participating in clinical efficacy trials of acupuncture.

PubMed

Enblom, Anna; Johnsson, Anna

2017-12-01

Many therapists practise PC6 acupuncture for emesis (nausea and vomiting) during pregnancy, different cancer therapies, palliative care, after surgery, or to induce relaxing effects in general. Knowledge of side effects is central to shared decision-making. To describe the type and frequency of side effects and the level of needle-induced pain during PC6 acupuncture. We included 1298 PC6 acupuncture treatments, delivered to 221 participants (77% women, mean age 52.5, range 18-91 years). The subjects had received genuine PC6 acupuncture, in one of two previous randomised controlled trials, aimed at inducing antiemetic (n=100, with 100 providing data on side effects and 94 on needle-induced pain, respectively) or relaxing (n=121, with 120 providing data) effects. Side effects during and after the acupuncture treatments were registered in structured treatment protocols and study diaries. No serious complications occurred. Side effects during the acupuncture sessions included minor bleeding in 5.0%, tiredness in 4.9%, numbness in 4.5% and dizziness in 1.4% of the 1298 treatments. After treatment, the mean proportions of participants reporting side effects each week were: tiredness 25.8%; feeling cold 17.8%; dizziness 9.7%; sweating 9.3%; haematoma 8.8%; and soreness at the needling sites 4.3%. Participants perceived the needling to be not painful (47.4% of participants), or mildly (39.1%), moderately (11.6%) or very painful (1.4%). Few side effects occurred and those that did were mild. Nearly 90% found PC6 acupuncture to be not painful or only mildly painful. Healthcare professionals may consider the observed levels of side effects when informing patients about side effects of PC6 acupuncture. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Side-gate modulation effects on high-quality BN-Graphene-BN nanoribbon capacitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yang; Chen, Xiaolong; Ye, Weiguang

High-quality BN-Graphene-BN nanoribbon capacitors with double side-gates of graphene have been experimentally realized. The double side-gates can effectively modulate the electronic properties of graphene nanoribbon capacitors. By applying anti-symmetric side-gate voltages, we observed significant upward shifting and flattening of the V-shaped capacitance curve near the charge neutrality point. Symmetric side-gate voltages, however, only resulted in tilted upward shifting along the opposite direction of applied gate voltages. These modulation effects followed the behavior of graphene nanoribbons predicted theoretically for metallic side-gate modulation. The negative quantum capacitance phenomenon predicted by numerical simulations for graphene nanoribbons modulated by graphene side-gates was not observed,more » possibly due to the weakened interactions between the graphene nanoribbon and side-gate electrodes caused by the Ga{sup +} beam etching process.« less

Recuperation of a severely debilitated wolf

USGS Publications Warehouse

Mech, L.D.; Seal, U.S.; Arthur, S.M.

1984-01-01

Opportunities are rare for determining the degree to which an animal can starve and still survive. Therefore we describe here an incident in which a wild wolf (Canis lupus) starved almost to death and was then restored to her former free-ranging state. The incident took place in northern Lake County, Minnesota

Eureka!

ERIC Educational Resources Information Center

Villano, Matt

2009-01-01

Academic technologists at Lynn University (Florida) learned the hard way just how important a disaster recovery plan can be. Back in 2005, when Hurricane Wilma walloped the region with driving rain and 120 mile-per-hour winds, the storm debilitated Lynn's IT department, causing damage and flooding that thwarted the campus network for nearly two…

77 FR 38323 - Proposed Extension of Existing Information Collection; Respirable Coal Mine Dust Sampling

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-27

...-9440 (voice); or 202-693-9441 (facsimile). SUPPLEMENTARY INFORMATION: I. Background The title of the..., silicosis, and chronic bronchitis, known collectively as ``black lung.'' These diseases are debilitating and... dust levels since 1970 and, consequently, the prevalence rate of black lung among coal miners, severe...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

Implications of the Physical Educator's Broadened Wellness Role

ERIC Educational Resources Information Center

Melville, Scott

2009-01-01

The United States is experiencing a health crisis because of poor dietary habits and insufficient physical activity. Unless something changes, more of the population will become overweight or obese and suffer from debilitating and life-threatening diseases. The federal government has responded by charging schools with the establishment of…

"Tackling Test Anxiety": A Group for College Students

ERIC Educational Resources Information Center

Damer, Diana E.; Melendres, Lauren T.

2011-01-01

Test anxiety is ubiquitous on college campuses and negatively impacts academic progress as well as overall mental and physical health. Some students develop test anxiety due to poor study skills, while others experience debilitating anxiety despite adequate preparation. In this article, a session-by-session description of a 4-week group…

Chronic Fatigue Syndrome: How Vulnerable Are Athletes?

ERIC Educational Resources Information Center

Eichner, Edward R.

1989-01-01

Discusses chronic fatigue syndrome as it affects elite athletes, noting that overtraining may mimic it. In some cases, athletes who have it perform exceedingly well in the face of debilitating fatigue. Among athletes and nonathletes, the cause and the mind-body connection are areas of controversy and research. (Author/SM)

21 CFR 312.85 - Phase 4 studies.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Phase 4 studies. 312.85 Section 312.85 Food and...-debilitating Illnesses § 312.85 Phase 4 studies. Concurrent with marketing approval, FDA may seek agreement from the sponsor to conduct certain postmarketing (phase 4) studies to delineate additional information...

21 CFR 312.85 - Phase 4 studies.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Phase 4 studies. 312.85 Section 312.85 Food and...-debilitating Illnesses § 312.85 Phase 4 studies. Concurrent with marketing approval, FDA may seek agreement from the sponsor to conduct certain postmarketing (phase 4) studies to delineate additional information...

Anxiety Management Training and Self-Control Desensitization: 15 Months Later.

ERIC Educational Resources Information Center

Deffenbacher, Jerry L.; Michaels, Ann C.

1981-01-01

A 15-month follow-up study found that anxiety management training and self-control desensitization groups continued to report significantly less debilitating test anxiety than the control group. Anxiety management training and self-control desensitization groups also reported significantly less nontargeted anxiety than controls on both measures of…

21 CFR 312.83 - Treatment protocols.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Treatment protocols. 312.83 Section 312.83 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR...-debilitating Illnesses § 312.83 Treatment protocols. If the preliminary analysis of phase 2 test results...

21 CFR 312.83 - Treatment protocols.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Treatment protocols. 312.83 Section 312.83 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR...-debilitating Illnesses § 312.83 Treatment protocols. If the preliminary analysis of phase 2 test results...

21 CFR 312.83 - Treatment protocols.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Treatment protocols. 312.83 Section 312.83 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR...-debilitating Illnesses § 312.83 Treatment protocols. If the preliminary analysis of phase 2 test results...

Multidisciplinary disease management in rheumatology.

PubMed

Oliver, Susan

2003-11-01

With an increasingly ageing population, the number of patients with osteoarthritis and rheumatoid arthritis is expected to rise. High-quality patient education and self-management are essential in these chronic debilitating conditions. A multidisciplinary team has produced a template to guide the assessment, treatment and holistic care of patients in primary care.

Reading Big Words: Instructional Practices to Promote Multisyllabic Word Reading Fluency

ERIC Educational Resources Information Center

Toste, Jessica R.; Williams, Kelly J.; Capin, Philip

2017-01-01

Poorly developed word recognition skills are the most pervasive and debilitating source of reading challenges for students with learning disabilities (LD). With a notable decrease in word reading instruction in the upper elementary grades, struggling readers receive fewer instructional opportunities to develop proficient word reading skills, yet…

Command and Control Across Space and Cyberspace Domains

DTIC Science & Technology

2016-02-16

debilitating impact on security, national economic security, national public health or safety, or any combination of those matters.”16).17 From Joint...Third, push control (if not command) to the theater or operational level. Returning to the inbound ICBM scenario proposed by Maj Gen Zabel and detailed

Reciprocal Mentoring Residencies... Better Transitions to Teaching

ERIC Educational Resources Information Center

Paris, Lisa

2010-01-01

The 2007 "Top of the Class" report on the Inquiry into Teacher Education in Australia found teacher induction failure and high attrition rates were endemic in most Australian states. Mentoring was advocated as an important mechanism for countering the debilitating drain attrition exerted on the profession (more than 30% within the first…

Case Series: Outbreak of Conversion Disorder among Amish Adolescent Girls.

ERIC Educational Resources Information Center

Cassady, Joslyn D.; Kirschke, David L.; Jones, Timothy F.; Craig, Allen S.; Bermudez, Ovidio B.; Schaffner, William

2005-01-01

Objective: Outbreak investigations are challenging in a cross-cultural context, and outbreaks of psychiatric disease are rare in any community. We investigated a cluster of unexplained debilitating illness among Amish girls. Method: We reviewed the medical records of cases, consulted with health care providers, performed active case finding,…

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

Family-Based Cognitive-Behavioral Treatment of Chronic Pediatric Headache and Anxiety Disorders: A Case Study

ERIC Educational Resources Information Center

Drake, Kelly L.; Ginsburg, Golda S.

2012-01-01

Background: Chronic pediatric headache disorders are pervasive, debilitating, and associated with high rates of comorbid anxiety disorders. The combination of headaches and anxiety presents unique challenges for clinicians. Cognitive behavioral therapy (CBT) is a promising treatment for pediatric headache, however, available treatments fail to…

Subjective experience and mental side-effects of antipsychotic treatment.

PubMed

Gerlach, J; Larsen, E B

1999-01-01

Many schizophrenic patients have a negative attitude towards antipsychotic drugs. This attitude is not only due to lack of insight into the disease, lack of recognition of the beneficial effects of the drugs, and to objective side-effects. The negative attitude is to a high degree due to mental side-effects and a sceptical opinion about antipsychotic medication in general. In a study of 53 chronic schizophrenic out-patients receiving maintenance depot antipsychotic treatment, we found that 60% were positive about the treatment, 32% were ambivalent and 8% had a negative attitude. Only 60% complained of side-effects, even though 94% had objective side-effects. Mental side-effects such as subjective akathisia, dysphoria and emotional indifference were most often observed by the patients, while hypokinesia and hyperkinesia were least noticed by them, but most often observed by the physician. No correlation was found between the patients' subjective assessment of their quality of life and the degree of psychosis and side-effects. With the new atypical antipsychotics this situation seems to be changing. These new drugs are primarily characterized by a lower level of motor extrapyramidal side-effects (EPS), and with fewer motor EPS, fewer mental EPS can be expected. In recent studies comparing the new antipsychotics with haloperidol, better effects have been observed with regard to negative symptoms and depression, and this may at least in part be a reflection of a lower level of mental side-effects of the atypical antipsychotics. This improved clinical profile of new antipsychotics is extremely valuable in the context of an integrated treatment in schizophrenia, consisting of early intervention, psychosocial rehabilitation and family/patient psycho-education.

Ayurveda for chemo-radiotherapy induced side effects in cancer patients.

PubMed

Metri, Kashinath; Bhargav, Hemant; Chowdhury, Praerna; Koka, Prasad S

2013-01-01

Chemotherapy drugs and radiotherapy are highly toxic and both damage adjacent healthy cells. Side effects may be acute (occurring within few weeks after therapy), intermediate or late (occurring months or years after the therapy). Some important side effects of chemotherapy are: nausea, vomiting, diarrhea, mucositis, alopecia, constipation etc; whereas radiation therapy though administered locally, can produce systemic side effects such as fatigue, anorexia, nausea, vomiting, alteration in the taste, sleep disturbance, headache, anemia, dry skin, constipation etc. Late complications of these therapies also include pharyngitis, esophagitis, laryngitis, persistent dysphagia, fatigue, hepatotoxicity, infertility and cognitive deficits. These arrays of side effects have a devastating effect on the quality of life of cancer survivors. Due to the inadequacy of most of the radio-protectors and chemo-protectors in controlling the side effects of conventional cancer therapy the complementary and alternative medicines have attracted the view of researchers and medical practitioners more recently. This review aims at providing a comprehensive management protocol of above mentioned chemo-radiotherapy induced side effects based on Ayurveda, which is an ancient system of traditional medicine practiced in Indian peninsula since 5000 BC. When the major side effects of chemo-radiotherapy are looked through an ayurvedic perspective, it appears that they are the manifestations of aggravated pitta dosha, especially under the group of disorders called Raktapitta (haemorrhage) or Raktadushti (vascular inflammation). Based on comprehensive review of ancient vedic literature and modern scientific evidences, ayurveda based interventions are put forth. This manuscript should help clinicians and people suffering from cancer to combat serious chemo-radiotherapy related side effects through simple but effective home-based ayurveda remedies. The remedies described are commonly available and safe. These simple ayurveda based solutions may act as an important adjuvant to chemo-radiotherapy and enhance the quality of life of cancer patients.

New perspectives in the treatment of body dysmorphic disorder

PubMed Central

Hong, Kevin; Nezgovorova, Vera; Hollander, Eric

2018-01-01

Body dysmorphic disorder (BDD) is a disabling illness with a high worldwide prevalence. Patients demonstrate a debilitating preoccupation with one or more perceived defects, often marked by poor insight or delusional convictions. Multiple studies have suggested that selective serotonin reuptake inhibitors and various cognitive behavioral therapy modalities are effective first-line treatments in decreasing BDD severity, relieving depressive symptoms, restoring insight, and increasing quality of life. Selective serotonin reuptake inhibitors have also recently been shown to be effective for relapse prevention. This review provides a comprehensive summary of the current understanding of BDD, including its clinical features, epidemiology, genetics, and current treatment modalities. Additional research is needed to fully elucidate the relationship between BDD and comorbid illnesses such as obsessive–compulsive-related disorders and depression and to develop therapies for refractory patients and those who have contraindications for pharmacological intervention. PMID:29636904

Dissatisfaction with opioid maintenance treatment partly explains reported side effects of medications.

PubMed

Muller, Ashley Elizabeth; Bjørnestad, Ronny; Clausen, Thomas

2018-03-29

Drop-out is a core problem in opioid maintenance treatment (OMT), but patients' reactions to and acceptance of the various OMT medications are insufficiently investigated. In Norway, there has been vocal patient resistance to the newest medication, buprenorphine-naloxone (BNX), and complaints have focused on the side effect profile. There has been no comparison of patient satisfaction and side effects of the three most common OMT medications. To compare patient satisfaction with OMT and side effects of BNX, buprenorphine monopreparate (BUP), and methadone (MET) as reported by patients. Data were drawn from a national peer-to-peer survey developed by a patient advocacy group. The survey engaged more than 1000 OMT patients, corresponding to one seventh of OMT patients in Norway. The associations between side effects, treatment satisfaction, and patient characteristics were tested in multinomial logistic regressions. High patient satisfaction with OMT overall was reported despite lower satisfaction with medication itself and widely prevalent side effects. Among each medication group, dissatisfaction with medications or OMT in general along with poor health status increased the relative risk ratio of reporting the heaviest side effect burden. MET users reported the highest side effect burden and BNX users the lightest, but BNX users were more dissatisfied with their medication. Side effects are a concern for nearly all OMT patients, and they do not appear to accumulate with age or length of treatment. BNX users' dissatisfaction with their medication is of particular concern, and expectations and preferences of medication may be influencing their dissatisfaction. Copyright © 2018. Published by Elsevier B.V.

Selective serotonin reuptake inhibitor discontinuation: side effects and other factors that influence medication adherence.

PubMed

Goethe, John W; Woolley, Stephen B; Cardoni, Alex A; Woznicki, Brenda A; Piez, Deborah A

2007-10-01

Patients with major depression discontinue taking their antidepressants for many reasons. Although side effects are often cited as the reason for discontinuation, few prospective studies have addressed this question, and none has specifically examined discontinuation in patients with severe depression. Inpatients and outpatients treated with a selective serotonin reuptake inhibitor for major depressive disorder were identified after admission. Three months later, patients were contacted and interviewed to determine antidepressant usage and the side effects experienced, including when these were experienced and their severity. Between October 2001 and April 2003, 406 English- or Spanish-speaking patients aged 18 to 75 years were followed up. One in 4 patients discontinued the index antidepressant. Among specific side effects noted, only "change in weight" and "anxiety" were significant predictors of discontinuation after controlling for confounders. Experiencing 1 or more "extremely" bothersome side effects was associated with more than a doubling of the risk of discontinuation, but the presence of side effects and side effects less severe than "extremely" bothersome were not significant predictors. There were no differences among selective serotonin reuptake inhibitor antidepressants in either the presence/absence of side effects or in the discontinuation rates. The results suggest that the contribution of side effects to antidepressant discontinuation is more complex than previously suggested. Disparate findings from earlier studies may reflect aspects of study design, such as examining populations whose severity of depression varied widely or not controlling for important confounding factors. Future research should separately examine high-risk groups (or control for severity of depression) and carefully rule out other potential contributors to discontinuation.

Effects of side lying on lung function in older individuals.

PubMed

Manning, F; Dean, E; Ross, J; Abboud, R T

1999-05-01

Body positioning exerts a strong effect on pulmonary function, but its effect on other components of the oxygen transport pathway are less well understood, especially the effects of side-lying positions. This study investigated the interrelationships between side-lying positions and indexes of lung function such as spirometry, alveolar diffusing capacity, and inhomogeneity of ventilation in older individuals. Nineteen nonsmoking subjects (mean age=62.8 years, SD=6.8, range=50-74) with no history of cardiac or pulmonary disease were tested over 2 sessions. The test positions were sitting and left side lying in one session and sitting and right side lying in the other session. In each of the positions, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), single-breath pulmonary diffusing capacity (DLCO/VA), and the slope of phase III (DN2%/L) of the single-breath nitrogen washout test to determine inhomogeneity of ventilation were measured. Compared with measurements obtained in the sitting position, FVC and FEV1 were decreased equally in the side-lying positions, but no change was observed in DLCO/VA or DN2%/L. Side-lying positions resulted in decreases in FVC and FEV1, which is consistent with the well-documented effects of the supine position. These findings further support the need for prescriptive rather than routine body positioning of patients with risks of cardiopulmonary compromise and the need to use upright positions in which lung volumes and capacities are maximized.

Effects and Side Effects of Flemish School Inspection

ERIC Educational Resources Information Center

Penninckx, Maarten; Vanhoof, Jan; De Maeyer, Sven; Van Petegem, Peter

2016-01-01

Despite the increased importance of school inspection in recent years, the current knowledge base does not provide a clear view on the effects and side effects of being inspected. More evidence is needed in more diverse educational contexts. This article responds to this need with a quantitative study on the effects and side effects of school…

Chemotherapy

MedlinePlus

... cells to get better. Because everyone's different, some people will have fewer side effects than others. Common side effects of chemo are ... infections easily. Medicines are available that can help people feel better if they have side effects from chemo. Doctors, nurses, and other members of ...

Predicting new drug indications from network analysis

NASA Astrophysics Data System (ADS)

Mohd Ali, Yousoff Effendy; Kwa, Kiam Heong; Ratnavelu, Kurunathan

This work adapts centrality measures commonly used in social network analysis to identify drugs with better positions in drug-side effect network and drug-indication network for the purpose of drug repositioning. Our basic hypothesis is that drugs having similar phenotypic profiles such as side effects may also share similar therapeutic properties based on related mechanism of action and vice versa. The networks were constructed from Side Effect Resource (SIDER) 4.1 which contains 1430 unique drugs with side effects and 1437 unique drugs with indications. Within the giant components of these networks, drugs were ranked based on their centrality scores whereby 18 prominent drugs from the drug-side effect network and 15 prominent drugs from the drug-indication network were identified. Indications and side effects of prominent drugs were deduced from the profiles of their neighbors in the networks and compared to existing clinical studies while an optimum threshold of similarity among drugs was sought for. The threshold can then be utilized for predicting indications and side effects of all drugs. Similarities of drugs were measured by the extent to which they share phenotypic profiles and neighbors. To improve the likelihood of accurate predictions, only profiles such as side effects of common or very common frequencies were considered. In summary, our work is an attempt to offer an alternative approach to drug repositioning using centrality measures commonly used for analyzing social networks.

[Cardiovascular side effects of non-steroidal anti-inflammatory drugs in the light of recent recommendations. Diclofenac is not more dangerous].

PubMed

Horváth, Viktor József; Tabák, Gy Ádám; Szabó, Gergely; Putz, Zsuzsanna; Koós, Csaba Géza; Lakatos, Péter

2015-03-29

Among their beneficial effects, non-steroidal anti-inflammatory drugs may also exert several side effects which depend on the dosage and the type of these medications. The most frequent gastrointestinal side effects usually develop shortly after the beginning of their administration, but others such as cardiovascular interactions (which are present much less frequently than gastrointestinal side effects) can also occur after the beginning of drug administration without a latency period. For a long-term treatment, non-steroidal anti-inflammatory drugs are most frequently used in the elderly population where patients typically have high cardiovascular risk and take other medicines, e.g. low dose acetylsalicylic acid that can interact with non-steroidal anti-inflammatory drugs; in this aspect diclofenac may cause less side effects. In this review, the authors briefly review cardiovascular side effects of non-steroidal anti-inflammatory drugs, the processes which potentially influence them, therapeutic consequences and their interaction with acetylsalicylic acid.

The impact of tamoxifen brand switch on side effects and patient compliance in hormone receptor positive breast cancer patients.

PubMed

Zeidan, B; Anderson, K; Peiris, L; Rainsbury, D; Laws, S

2016-10-01

In 2006 Nolvadex was discontinued and replaced by a variety of alternative generic tamoxifen brands for the adjuvant treatment of breast cancer. Anecdotally, patients are switching brands and taking alternative medications to reduce treatment related symptoms. Nevertheless, more severe side effects may equate to better relapse prevention. This study evaluates generic tamoxifen adherence and its correlation with side effects and brand switch. Consecutive disease free ER positive patients (stage I-III) were invited to respond to a questionnaire. 165 of 327 questionnaires were returned (50% response). Pearson's Chi Square test was used for data analysis. 63 patients (38%) reported a switch between generic tamoxifen. 59% of all patients experienced side effects associated with tamoxifen treatment of which 53% were severe. Patients experiencing differential symptoms dependent on tamoxifen brand reported more severe side effects (p = 0.02). Non-prescribed supplements were taken by 42% of all patients with no significant improvement in climacteric symptoms (p = 0.05). The concomitant use of SSRIs appeared to have no effect on symptoms. A significant number of patients considered discontinuing tamoxifen because of the side effects (p = 0.001), yet this did not translate into discontinuation or non-adherence (p = 0.8 and 0.08 respectively). Severe tamoxifen side effects are commonly experienced by breast cancer patients and can be significantly altered by change in tamoxifen brand. Most patients will continue to take tamoxifen, despite side effects to avoid cancer relapse. Supplementation and antidepressants did not improve tamoxifen related side effects in our cohort. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Influencing factors of dysmenorrhoea among hospital nurses: a questionnaire survey in Taiwan.

PubMed

Chiu, Min-Hui; Hsieh, Hsiu-Fen; Yang, Yi-Hsin; Chen, Huei-Mein; Hsu, Su-Chen; Wang, Hsiu-Hung

2017-12-19

Nurses are at high risk of dysmenorrhoea while working with patients. The study objectives were to: (1) describe the demographic and menstruation characteristics of dysmenorrhoea, knowledge about dysmenorrhoea and menstrual attitudes towards menstruation among dysmenorrhoeal and non-dysmenorrhoeal hospital nurses; (2) identify significant differences between the groups; and (3) examine factors influencing dysmenorrhoea. This cross-sectional survey used a structured questionnaire, administered at two hospitals in southern Taiwan. Participants included hospital nurses at least 18 years of age who agreed to participate. All participants were recruited through random sampling. The questionnaire included demographic data, the Dysmenorrhoea Knowledge Scale and Menstrual Attitude Scale (MAS). A total of 420 nurses completed the questionnaire. Among them, 297 (70.7%) had experienced dysmenorrhoea in the past 6 months and 123 (29.3%) had not. Significant differences in age (P<0.001), marital status (P<0.001), childbearing status (P<0.001), age at menarche (P<0.05) and rotating three shift ratio (P<0.05) were identified between the dysmenorrhoea and non-dysmenorrhoea groups. Analysis of the MAS results revealed significant differences between the groups regarding consideration of menstruation as a debilitating (P<0.001) or bothersome event (P<0.05), anticipation and prediction of menstruation onset (P<0.01) and denial of any effects from menstruation (P<0.001). Results of the multiple logistic regression showed that predictive factors included age <40 years (4.46 vs 1.00), working three shift rotations (2.07 vs 1.00), marital status (2.59 vs 1.00), acknowledging menstruation as a debilitating event (2.72 vs 1.00) and denial of effects from menstruation (2.59 vs 1.00). These findings could help nursing managers to create a caring and friendly work environment for hospital nurses at risk of dysmenorrhoea. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Influencing factors of dysmenorrhoea among hospital nurses: a questionnaire survey in Taiwan

PubMed Central

Chiu, Min-Hui; Hsieh, Hsiu-Fen; Yang, Yi-Hsin; Chen, Huei-Mein; Hsu, Su-Chen

2017-01-01

Objectives Nurses are at high risk of dysmenorrhoea while working with patients. The study objectives were to: (1) describe the demographic and menstruation characteristics of dysmenorrhoea, knowledge about dysmenorrhoea and menstrual attitudes towards menstruation among dysmenorrhoeal and non-dysmenorrhoeal hospital nurses; (2) identify significant differences between the groups; and (3) examine factors influencing dysmenorrhoea. Methods This cross-sectional survey used a structured questionnaire, administered at two hospitals in southern Taiwan. Participants included hospital nurses at least 18 years of age who agreed to participate. All participants were recruited through random sampling. The questionnaire included demographic data, the Dysmenorrhoea Knowledge Scale and Menstrual Attitude Scale (MAS). Results A total of 420 nurses completed the questionnaire. Among them, 297 (70.7%) had experienced dysmenorrhoea in the past 6 months and 123 (29.3%) had not. Significant differences in age (P<0.001), marital status (P<0.001), childbearing status (P<0.001), age at menarche (P<0.05) and rotating three shift ratio (P<0.05) were identified between the dysmenorrhoea and non-dysmenorrhoea groups. Analysis of the MAS results revealed significant differences between the groups regarding consideration of menstruation as a debilitating (P<0.001) or bothersome event (P<0.05), anticipation and prediction of menstruation onset (P<0.01) and denial of any effects from menstruation (P<0.001). Results of the multiple logistic regression showed that predictive factors included age <40 years (4.46 vs 1.00), working three shift rotations (2.07 vs 1.00), marital status (2.59 vs 1.00), acknowledging menstruation as a debilitating event (2.72 vs 1.00) and denial of effects from menstruation (2.59 vs 1.00). Conclusions These findings could help nursing managers to create a caring and friendly work environment for hospital nurses at risk of dysmenorrhoea. PMID:29259057

Problems of long-term spinal opioid treatment in advanced cancer patients.

PubMed

Mercadante, S

1999-01-01

Epidural and intrathecal techniques are well established techniques in cancer pain. However, several questions remain unresolved. The several problems of long-term spinal opioid treatment in advance cancer patients were reviewed. Indications for the use of spinal opioids include patients treated by systemic opioids with effective pain relief but with unacceptable side effects, or unsuccessful treatment with sequential strong opioid drug trials despite escalating doses. Therefore, the previous aggressive treatment with systemic opioids would leave as failures patients with difficult pain syndromes unresponsive to opioids. The choice of external or totally implanted delivery systems is based on different clinical considerations. The use of externalized tunneled intrathecal catheters has not been associated with higher rates of complications and is easier to place and use at home in debilitated patients late in the course of their disease. The intrathecal administration has a lower incidence of catheter occlusion, lower malfunctioning rate, lower dose requirement, and more effective pain control. Due to the lower daily doses and volumes, intrathecal treatment proved to be more suitable for treatment at home by a continuous infusion than the epidural treatment. Advantages of infusion techniques are more evident when using local anesthetics, since intermittent administration of bupivacaine often results in motor paralysis and hemodynamic instability. Morphine is the opioid of choice. An epidural dose of 10% of the systemic dose is often used. However, intrathecal administration of opioids and bupivacaine may substantially improve pain relief in patients unresponsive to high epidural doses of these drugs, Bupivacaine-induced adverse effects, including sensory deficits, motor complaints, signs of autonomic dysfunction or neurotoxicity have been reported to not occur with bupivacaine doses less than 30-60 mg/day. Adjuvant drugs may further improve analgesia. Different ranges of technical complication rates have been reported in the literature, most of them being associated with epidural catheters. Subcutaneous tunneling and fixation of the catheter, bacterial filters, minimum changes of tubings, careful exit site care weekly, site protection and monitoring of any sign of infection to prevent infection, and training for family under supervision, are recommended. Areas for additional research include the use of spinal adjuvants, the ideal spinal morphine-bupivacaine ratio. methods to improve spinal opioid responsiveness and long-term catheter management with appropriate home care programs.

MO-D-BRF-01: Pediatric Treatment Planning II: The PENTEC Report On Normal Tissue Complications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Constine, L; Hodgson, D; Bentzen, S

With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy may cause debilitating or even fatal ‘late effects’ that are critical to understand, mitigate, or prevent. QUANTEC identified the uncertainties relating to side-effects of adult treatments, but this is more complicated for children in whom a mosaic of tissues develops at different rates and temporal sequences. Childhood cancer survivors have long life expectancy and may develop treatmentinduced secondary cancers and severe organ/tissue injury decades after treatment. Collaborative long-term observational studies and clinical research programs for survivors of pediatric and adolescent cancer provide some dose-responsemore » data for follow-up periods exceeding 40 years. Data analysis is challenging due to the influence of both therapeutic and developmental variables. PENTEC is a group of radiation oncologists, pediatric oncologists, subsepcialty physicians, medical physicists, biomathematic modelers/statisticians, and epidemiologists charged with conducting a critical synthesis of existing literature aiming to: critically analyze radiation dose-volume effects on normal tissue tolerances as a function of age/development in pediatric cancer patients in order to inform treatment planning and improve outcomes for survivors; describe relevant physics issues specific to pediatric radiotherapy; propose dose-volumeoutcome reporting standards to improve the knowledge base to inform future treatment guidelines. PENTEC has developed guidelines for systematic literature reviews, data extraction tolls and data analysis. This education session will discuss:1. Special considerations for normal tissue radiation response of children/adolescents, e.g. the interplay between development and radiotherapy effects.2. Epidemiology of organ/tissue injuries and secondary cancers.3. Exploration of dose-response differences between children and adults4. Methodology for literature review, data mining of outcomes databases, and NTCP or longitudinal modeling of doseresponse. 5. PENTEC goals and timetable. Learning Objectives: Understand important differences between normal tissue effects of radiation therapy in pediatric and adult patients. Be able to identify situations where there is ‘interplay’ between organ development and radiation-induced complications. Identify methods to systematically extract quantitative dose-volumeresponse relationships from existing outcomes databases. Provide guidance for the medical physicist to properly understand, implement, guide and control contemporary technology and applications in pediatric radiation oncology.« less

The Association of Long-term Treatment-related Side Effects With Cancer-specific and General Quality of Life Among Prostate Cancer Survivors

PubMed Central

Davis, Kimberly M.; Kelly, Scott P.; Luta, George; Tomko, Catherine; Miller, Anthony B.; Taylor, Kathryn L.

2018-01-01

OBJECTIVE To examine the association between treatment-related side effects and cancer-specific and general quality of life (QOL) among long-term prostate cancer survivors. MATERIALS AND METHODS Within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we conducted telephone interviews with prostate cancer survivors (N = 518) who were 5-10 years after diagnosis. We assessed demographic and clinical information, sexual, urinary, and bowel treatment-related side effects (Expanded Prostate Cancer Index Composite), cancer-specific QOL (Functional Assessment of Cancer Therapy—total score), and general QOL (the Medical Outcomes Study Short Form 12’s physical and mental subscales). RESULTS Participants were aged 74.6 years on average, primarily White (88.4%), and married (81.7%). Pearson correlation coefficients between the 3 treatment-related side effect domains (urinary, sexual, and bowel) and QOL ranged between 0.14 and 0.42 (P <.0001). Multivariable linear regression analyses revealed that poorer urinary and sexual functioning and greater bowel side effects were independently associated with poorer cancer-specific QOL (P <.0001). Bowel and urinary functions were also associated with poorer general QOL on the Medical Outcomes Study Short Form 12’s physical component summary and mental component summary (P <.05). Bowel side effects demonstrated the strongest association with all QOL outcomes. CONCLUSION Treatment-related side effects persisted for up to 10 years after diagnosis and continued to be associated with men’s QOL. These results suggest that each of the treatment-related side effects was independently associated with cancer-specific QOL. Compared with the other Expanded Prostate Cancer Index Composite domains, bowel side effects had the strongest association with cancer-specific and general QOL. These associations emphasize the tremendous impact that bowel side effects continue to have for men many years after their initial diagnosis. PMID:24975711

Consumer confusion between prescription drug precautions and side effects.

PubMed

Amoozegar, Jacqueline B; Rupert, Douglas J; Sullivan, Helen W; O'Donoghue, Amie C

2017-06-01

Multiple studies have identified consumers' difficulty correctly interpreting risk information provided about prescription drugs, whether in printed format or online. This study's purpose was to explore whether consumers can distinguish between prescription drug precautions and side effects presented on brand-name drug websites. Participants (n=873) viewed fictitious drug websites that presented both precautions and side effects for one of four drugs, and they completed a survey assessing recall and comprehension. We coded open-ended recall data to identify whether drug precautions were mentioned and, if so, how they were interpreted. Approximately 15% of participants mentioned at least one drug precaution. The majority (59.7%) misinterpreted precautions as potential side effects. Participants who misinterpreted precautions rated the drugs as significantly more likely to cause side effects than participants who accurately interpreted the precautions. Age, education, literacy, and other factors did not appear to predict precaution interpretation. At least some consumers are likely to interpret precautions on drug websites as potential side effects, which might affect consumer preferences, treatment decisions, and medication safety. Healthcare providers should be aware of this potential confusion, assess patients' understanding of precautions and potential side effects, and address any misunderstandings. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Ocular side-effects associated with imatinib mesylate (Gleevec).

PubMed

Fraunfelder, Frederick W; Solomon, Jonathan; Druker, Brian J; Esmaeli, Bita; Kuyl, Jennifer

2003-08-01

This retrospective case series describes ocular side-effects associated with imatinib mesylate (Gleevec) and the clinical characteristics of these adverse reactions. A chart review of 104 patients on imatinib mesylate therapy from Oregon Health & Science University's Cancer Center were studied with regard to ocular side-effects. In addition, spontaneous reports from the Food and Drug Administration, the World Health Organization, and the National Registry of Drug-Induced Ocular Side-Effects databases were reviewed, including a Medline literature search. Seventy-three (70%) of the patients at OHSU developed periorbital edema and 19 patients (18%) developed epiphora after receiving imatinib mesylate. Average dose was 407.5+/-60 mg. Periorbital edema occurred an average of 68+/-48 days after initiation of therapy. WHO classification of side-effects is as follows: certain: periorbital edema; probable: epiphora; possible: extraocular muscle palsy, ptosis, blepharoconjunctivitis; unlikely: glaucoma, papilledema, retinal hemorrhage, photosensitivity, abnormal vision, and increased intraocular pressure. Periorbital edema and epiphora are the two most common ocular side-effects related to imatinib mesylate therapy. Clinical characteristics of imatinib mesylate induced periorbital edema are described. Management of ocular side-effects is conservative except in very rare cases of visually significant periorbital edema.

Fast image decompression for telebrowsing of images

NASA Technical Reports Server (NTRS)

Miaou, Shaou-Gang; Tou, Julius T.

1993-01-01

Progressive image transmission (PIT) is often used to reduce the transmission time of an image telebrowsing system. A side effect of the PIT is the increase of computational complexity at the viewer's site. This effect is more serious in transform domain techniques than in other techniques. Recent attempts to reduce the side effect are futile as they create another side effect, namely, the discontinuous and unpleasant image build-up. Based on a practical assumption that image blocks to be inverse transformed are generally sparse, this paper presents a method to minimize both side effects simultaneously.

A potential role for adjunctive vitamin D therapy in the management of weight gain and metabolic side effects of second-generation antipsychotics

PubMed Central

Nwosu, Benjamin U.; Meltzer, Bruce; Maranda, Louise; Ciccarelli, Carol; Reynolds, Daniel; Curtis, Laura; King, Jean; Frazier, Jean A.; Lee, Mary M.

2014-01-01

Second-generation antipsychotic (SGA) medications introduced about 20 years ago are increasingly used to treat psychiatric illnesses in children and adolescents. There has been a five-fold increase in the use of these medications in U.S. children and adolescents in the past decade. However, there has also been a parallel rise in the incidence of side effects associated with these medications, such as obesity, dyslipidemia, insulin resistance, and diabetes mellitus. Despite the severity of these complications and their financial impact on the national healthcare budget, there is neither a clear understanding of the mechanisms contributing to these side effects nor the best ways to address them. Studies that examined lifestyle modification and pharmaceutical agents have yielded mixed results. Therefore, clinical studies using agents, such as vitamin D, which are inexpensive, readily available, with low side effects profile, and have mechanisms to counteract the metabolic side effects of SGA agents, are warranted. Vitamin D is a prohormone with skeletal and extraskeletal properties that could potentially reduce the severity of these metabolic side effects. Its role as an adjunctive therapy for the management of metabolic side effects of SGA agents has not been adequately studied. Effective strategies to curb these side effects will improve the overall health of youths with psychiatric illnesses who receive SGAs. Herein we present a pilot study on the use of vitamin D in patients on treatment with SGAs. PMID:22145446

Choreatic Side Effects of Deep Brain Stimulation of the Anteromedial Subthalamic Nucleus for Treatment-Resistant Obsessive-Compulsive disorder.

PubMed

Mulders, Anne E P; Leentjens, Albert F G; Schruers, Koen; Duits, Annelien; Ackermans, Linda; Temel, Yasin

2017-08-01

Patients with treatment-resistant obsessive-compulsive disorder (OCD) are potential candidates for deep brain stimulation (DBS). The anteromedial subthalamic nucleus (STN) is among the most commonly used targets for DBS in OCD. We present a patient with a 30-year history of treatment-resistant OCD who underwent anteromedial STN-DBS. Despite a clear mood-enhancing effect, stimulation caused motor side effects, including bilateral hyperkinesia, dyskinesias, and sudden large amplitude choreatic movements of arms and legs when stimulating at voltages greater than approximately 1.5 V. DBS at lower amplitudes and at other contact points failed to result in a significant reduction of obsessions and compulsions without inducing motor side effects. Because of this limitation in programming options, we decided to reoperate and target the ventral capsule/ventral striatum (VC/VS), which resulted in a substantial reduction in key obsessive and compulsive symptoms without serious side effects. Choreatic movements and hemiballismus have previously been linked to STN dysfunction and have been incidentally reported as side effects of DBS of the dorsolateral STN in Parkinson disease (PD). However, in PD, these side effects were usually transient, and they rarely interfered with DBS programming. In our patient, the motor side effects were persistent, and they made optimal DBS programming impossible. To our knowledge, such severe and persistent motor side effects have not been described previously for anteromedial STN-DBS. Copyright © 2017 Elsevier Inc. All rights reserved.

Measurement of Side Effects of Drugs

PubMed Central

Huskisson, E. C.; Wojtulewski, J. A.

1974-01-01

In a clinical trial of two antirheumatic agents two methods of collection of side effects were used, one with and the other without a check list of possible symptoms. Findings suggested that the use of a check list interfered with the collection of side effects. Known side effects of aspirin—tinnitus, deafness, and gastrointestinal disturbance—were more efficiently shown and symptoms not included in the check list were more likely to be reported when a check list was not used. PMID:4853118

Comparison of hair removal efficacy and side effect of neodymium:Yttrium-aluminum-garnet laser and intense pulsed light systems (18-month follow-up).

PubMed

Szima, Georgina Zita; Janka, Eszter Anna; Kovács, Anikó; Bortély, Blanka; Bodnár, Edina; Sawhney, Irina; Szabó, Éva; Remenyik, Éva

2017-06-01

Photothermal destruction of hair shaft melanin with intense pulsed light (IPL) and neodymium:yttrium-aluminum-garnet (Nd:YAG) laser has become an effective treatment of hair removal. Our aim was to compare efficacy, satisfactory levels, safety, and side effects of Nd:YAG and IPL in hair reduction. This was a prospective randomized intrapatient, right-left, assessor-blinded comparison of Nd:YAG vs IPL. There were 38 volunteers recruited. Seven sessions were performed. Hair count, efficacy, and side effects were compared before and after each treatment and 6 months after the last treatment. In respect of 12 volunteers, we have examined the reduction in hair after 18 months. Initially, there was no significant difference between the numbers of hair follicles. There was significant hair reduction after each treatment on the Nd:YAG-treated side. The hair reduction became significant after the third treatment with IPL. Comparison of the efficacy of the two devices on each visits showed no significant difference. There was statistically lower pain score on the IPL-treated side and statistically higher erythema, burning sensation, and edema on the Nd:YAG-treated side. Statistically lower side effect score was observed on the IPL-treated side. Eight months after the last treatment, there was significant hair reduction both on the Nd:YAG and on the IPL-treated side, and there was no difference between the efficacy. The patient satisfaction scores were higher with the IPL. Unwanted hair can be reduced by both systems safely and effectively; however, IPL has less side effects and higher satisfaction scores. © 2017 Wiley Periodicals, Inc.

Side effects during subcutaneous immunotherapy in children with allergic diseases.

PubMed

Tophof, Max A; Hermanns, Anne; Adelt, Thomas; Eberle, Peter; Gronke, Christine; Friedrichs, Frank; Knecht, Roland; Mönter, Ernst; Schöpfer, Helmut; Schwerk, Nicolaus; Steinbach, Jörg; Umpfenbach, Hans-Ulrich; Weißhaar, Christian; Wilmsmeyer, Brigitte; Bufe, Albrecht

2018-05-01

Allergen-specific immunotherapy is the only causal form of therapy for IgE-mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. A non-interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Women with breast cancer report substantially more disease- and treatment-related side or late effects than registered by clinical oncologists: a cross-sectional study of a standard follow-up program in an oncological department.

PubMed

Ellegaard, Mai-Britt Bjørklund; Grau, Cai; Zachariae, Robert; Jensen, Anders Bonde

2017-08-01

Follow-up after breast cancer treatment is standard due to the risk of development of new primary cancers and recurrent disease. The aim of the present study was to evaluate a standard follow-up program in an oncological department by assessing: (1) Symptoms or signs of new primary cancer or recurrent disease, (2) Disease- and treatment-related physical and psychosocial side or late effects, and (3) relevant actions by oncology staff. In a cross-sectional study, 194 women who came for follow-up visit after treatment for primary surgery were included. The clinical oncologists registered symptoms and signs of recurrent disease or new primary cancer. Side or late effects were both assessed by patient and the clinical oncologists. Loco-regional or distant signs of recurrent disease were suspected in eight (5%) patients. Further examinations revealed no disease recurrence. Most patients (93%) reported some degree of side or late effects. Statistically significant more side or late effects were reported by the women (average: 6.9) than registered by the clinical oncologists (average: 2.4), p < 0.001. The three most often patient-reported side or late effects were hot flushes (35%), fatigue (32%), and sleep disturbance (31%). None of the scheduled or additional visits resulted in detection of recurrent disease. Furthermore, the majority of patients reported side or late effects. Statistically significant more women reported side or late effects than registered by the clinical oncologists. This suggests the need for rethinking of the follow-up programs with more emphasis upon side or late effects of the treatment.

Specific expectancies are associated with symptomatic outcomes and side effect burden in a trial of chamomile extract for Generalized Anxiety Disorder

PubMed Central

Keefe, John R.; Amsterdam, Jay; Li, Qing S; Soeller, Irene; DeRubeis, Robert; Mao, Jun J

2017-01-01

Objective Patient expectancies are hypothesized to contribute to the efficacy and side effects of psychiatric treatments, but little research has investigated this hypothesis in the context of psychopharmacological therapies for anxiety. We prospectively investigated whether expectancies predicted efficacy and adverse events in oral therapy for Generalized Anxiety Disorder (GAD), controlling for confounding patient characteristics correlating with outcomes. Methods Expectancies regarding treatment efficacy and side effects were assessed at baseline of an eight week open-label phase of a trial of chamomile for Generalized Anxiety Disorder (GAD). The primary outcome was patient-reported GAD-7 scores, with clinical response and treatment-emergent side-effects as secondary outcomes. Expectancies were used to predict symptomatic and side-effect outcomes. Results Very few baseline patient characteristics predicted either type of expectancy. Controlling for a patient’s predicted recovery based on their baseline characteristics, higher efficacy expectancies at baseline predicted greater change on the GAD-7 (adjusted β = −0.19, p = 0.011). Efficacy expectancies also predicted a higher likelihood of attaining clinical response (adjusted odds ratio = 1.69, p = 0.002). Patients with higher side effect expectancies reported more side effects (adjusted log expected count = 0.26, p = 0.038). Efficacy expectancies were unrelated to side effect reports (log expected count = −0.05, p = 0.680), and side effect expectancies were unrelated to treatment efficacy (β = 0.08, p = 0.306). Conclusions Patients entering chamomile treatment for GAD with more favorable self-generated expectancies for the treatment experience greater improvement and fewer adverse events. Aligning patient expectancies with treatment selections may optimize outcomes. PMID:27716513

Psychedelics as Medicines: An Emerging New Paradigm.

PubMed

Nichols, D E; Johnson, M W; Nichols, C D

2017-02-01

Scientific interest in serotonergic psychedelics (e.g., psilocybin and LSD; 5-HT 2A receptor agonists) has dramatically increased within the last decade. Clinical studies administering psychedelics with psychotherapy have shown preliminary evidence of robust efficacy in treating anxiety and depression, as well as addiction to tobacco and alcohol. Moreover, recent research has suggested that these compounds have potential efficacy against inflammatory diseases through novel mechanisms, with potential advantages over existing antiinflammatory agents. We propose that psychedelics exert therapeutic effects for psychiatric disorders by acutely destabilizing local brain network hubs and global network connectivity via amplification of neuronal avalanches, providing the occasion for brain network "resetting" after the acute effects have resolved. Antiinflammatory effects may hold promise for efficacy in treatment of inflammation-related nonpsychiatric as well as potentially for psychiatric disorders. Serotonergic psychedelics operate through unique mechanisms that show promising effects for a variety of intractable, debilitating, and lethal disorders, and should be rigorously researched. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Role of Vitamin D in Osteoarthritis: Molecular, Cellular, and Clinical Perspectives

PubMed Central

Honsawek, Sittisak

2015-01-01

Osteoarthritis is a debilitating and degenerative disease which affects millions of people worldwide. The causes and mechanisms of osteoarthritis remain to be fully understood. Vitamin D has been hypothesised to play essential roles in a number of diseases including osteoarthritis. Many cell types within osteoarthritic joints appear to experience negative effects often at increased sensitivity to vitamin D. These findings contrast clinical research which has identified vitamin D deficiency to have a worryingly high prevalence among osteoarthritis patients. Randomised-controlled trial is considered to be the most rigorous way of determining the effects of vitamin D supplementation on the development of osteoarthritis. Studies into the effects of low vitamin D levels on pain and joint function have to date yielded controversial results. Due to the apparent conflicting effects of vitamin D in knee osteoarthritis, further research is required to fully elucidate its role in the development and progression of the disease as well as assess the efficacy and safety of vitamin D supplementation as a therapeutic strategy. PMID:26229532

An HDAC-dependent epigenetic mechanism that enhances the efficacy of the antidepressant drug fluoxetine

PubMed Central

Schmauss, C.

2015-01-01

Depression is a prevalent and debilitating psychiatric illnesses. However, currently prescribed antidepressant drugs are only efficacious in a limited group of patients. Studies on Balb/c mice suggested that histone deacetylase (HDAC) inhibition may enhance the efficacy of the widely-prescribed antidepressant drug fluoxetine. This study shows that reducing HDAC activity in fluoxetine-treated Balb/c mice leads to robust antidepressant and anxiolytic effects. While reducing the activity of class I HDACs 1 and 3 led to antidepressant effects, additional class II HDAC inhibition was necessary to exert anxiolytic effects. In fluoxetine-treated mice, HDAC inhibitors increased enrichment of acetylated histone H4 protein and RNA polymerase II at promotor 3 of the brain-derived neurotrophic factor (Bdnf) gene and increased Bdnf transcription from this promotor. Reducing Bdnf-stimulated tropomyosin kinase B receptor activation in fluoxetine-treated mice with low HDAC activity abolished the behavioral effects of fluoxetine, suggesting that the HDAC-triggered epigenetic stimulation of Bdnf expression is critical for therapeutic efficacy. PMID:25639887

[Extrapyramidal side-effects: avoidance, diagnosis and treatment].

PubMed

Fleischhacker, W Wolfgang; Widschwendter, Christian

2005-04-01

Acute extrapyramidal side-effects (EPS) are a common phenomenon of treatment with antipsychotics. They are associated with a substantial reduction of the patient's quality of life and of compliance with the treatment. This article gives an overview of the different forms of EPS. It outlines strategies to avoid these side-effects and discusses problems in diagnosis and treatment. In comparison to conventional compounds, the clearest advantage of new generation antipsychotics is a reduced risk of the occurrence of extrapyramidal side-effects (EPS). Many studies have found that newer antipsychotics have a lesser propensity to causes EPS. Nevertheless, there are some conflicting results on this topic. This article discusses some of these results and sheds light on methodological problems in the evaluation of side-effects of antipsychotic treatment.